Change search
Refine search result
123 1 - 50 of 119
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Abu-Elyazeed, R R
    et al.
    Heineman, T
    Dubin, G
    Fourneau, M
    Leroux-Roels, I
    Leroux-Roels, G
    Richardus, J H
    Ostergaard, L
    Diez-Domingo, J
    Poder, A
    Van Damme, P
    Romanowski, B
    Blatter, M
    Silfverdal, S A
    Berglund, J
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Cunningham, A L
    Flodmark, C E
    Tragiannidis, A
    Dobson, S
    Olafsson, J
    Puig-Barbera, J
    Mendez, M
    Barton, S
    Bernstein, D
    Mares, J
    Ratner, P
    Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial.2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, no 51, p. 6136-6043Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.

    METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.

    RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.

    CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

  • 2. Abu-Elyazeed, R R
    et al.
    Heineman, T
    Dubin, G
    Fourneau, M
    Leroux-Roels, I
    Leroux-Roels, G
    Richardus, J H
    Ostergaard, L
    Diez-Domingo, J
    Poder, A
    Van Damme, P
    Romanowski, B
    Blatter, M
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berglund, J
    Josefsson, A
    Cunningham, A L
    Flodmark, C E
    Tragiannidis, A
    Dobson, S
    Olafsson, J
    Puig-Barbera, J
    Mendez, M
    Barton, S
    Bernstein, D
    Mares, J
    Ratner, P
    Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, no 51, p. 6136-6143Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.

    METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.

    RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.

    CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

  • 3. Andersson, Charlotta Rydgard
    et al.
    Vene, Sirkka
    Insulander, Mona
    Lindquist, Lars
    Lundkvist, Åke
    Günther, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Vaccine failures after active immunisation against tick-borne encephalitis2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 16, p. 2827-2831Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis (TBE) is a major disease of the central nervous system in Europe and is endemic in Sweden with about 200 notified cases annually. The far most effective protective measure against TBE is active immunisation. The vaccines available today induce a high degree of protection in field studies. However, vaccine failures have occasionally been reported and may be overlooked due to different, and sometimes confusing, antibody kinetics in vaccinees with TBEV infection. In this study, 27 patients with clinical and serological evidences of TBE despite adequate immunisation are presented. Vaccination failure is characterized by a slow, and initially non-detectable, development of the specific TBEV-IgM response, seen together with a rapid rise of IgG and neutralising antibodies in serum. The majority (70%) of the patients were more than 50 years of age, which may implicate a need for a modified immunisation strategy in the elderly.

  • 4.
    Arama, Charles
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Assefaw-Redda, Yohannes
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Rodriguez, Ariane
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Corradin, Giampietro
    Kaufmann, Stefan H. E.
    Reece, Stephen T.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guerin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 27, p. 4040-4045Article in journal (Refereed)
    Abstract [en]

    Background: Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines. Results: In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-gamma and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses. Conclusion: The increased IFN-gamma-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.

  • 5.
    Arama, Charles
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Waseem, Shahid
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Assefaw-Redda, Yohannes
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    You, Liya
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Rodriguez, Ariane
    Radošević, Katarina
    Goudsmit, Jaap
    Kaufmann, Stefan H E
    Reece, Stephen T
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    A recombinant Bacille Calmette-Guerin construct expressing the Plasmodium falciparum circumsporozoite protein enhances dendritic cell activation and primes for circumsporozoite-specific memory cells in BALB/c mice2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 37, p. 5578-5584Article in journal (Refereed)
    Abstract [en]

    A protective malaria vaccine may induce both high levels of neutralising antibodies and strong T-cell responses. The Plasmodium falciparum circumsporozoite protein (CSp) is a leading pre-erythrocytic vaccine candidate. CSp is a week immunogen per se, but Mycobacterium bovis Bacille Calmette-Guérin (BCG) has excellent adjuvant activity and has been utilized as a vector to deliver heterologous vaccine candidate antigens. It is safe in immunocompetent individuals and inexpensive to produce. We assessed in vitro and in vivo a recombinant BCG-expressing CSp (BCG-CS) as malaria vaccine candidate. Immunisation of BALB/c mice with BCG-CS augmented numbers of dendritic cells (DCs) in draining lymph nodes and in the spleen. The activation markers MHC-class-II, CD40, CD80 and CD86 on DCs were significantly upregulated by BCG-CS as compared to wild-type BCG (wt-BCG). In vitro stimulation of bone marrow-derived DCs and macrophages with BCG-CS induced IL-12 and TNF-α production. BCG-CS induced higher phagocytic activity in macrophages as compared to wt-BCG. Immunogenicity studies show that BCG-CS induced CS-specific antibodies and IFN-γ-producing memory cells. In conclusion, BCG-CS is highly efficient in activating antigen-presenting cells (APCs) for priming of adaptive immunity. Implications for the rational design of novel vaccines against malaria and TB, the two major devastating poverty-related diseases, are discussed.

  • 6.
    Arko-Mensah, John
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Rahman, Muhammad J
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Dégano, Irene R
    Chuquimia, Olga D
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Fotio, Agathe L
    Garcia, Irene
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Resistance to mycobacterial infection: a pattern of early immune responses leads to a better control of pulmonary infection in C57BL/6 compared with BALB/c mice.2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 52, p. 7418-27Article in journal (Refereed)
    Abstract [en]

    In this study, we have compared the immunological responses associated with early pulmonary mycobacterial infection in two mouse strains, BALB/c and C57BL/6 known to exhibit distinct differences in susceptibility to infection with several pathogens. We infected mice via the intranasal route. We have demonstrated that BALB/c was less able to control mycobacterial growth in the lungs during the early phase of pulmonary infection. Our results showed that during the early phase (day 3 to week 1), BALB/c mice exhibited a delay in the production of TNF and IFN-gamma in the lungs compared to C57BL/6 mice. Levels of IL-12 and soluble TNF receptors (sTNFR) were comparable between the mouse strains. The cellular subset distribution in these mice before and after infection showed a higher increase in CD11b+ cells in the lungs of C57BL/6, compared to BALB/c as early as day 3 postinfection. At early time points, higher levels of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein 1 (MIP)-alpha were detected in C57BL/6 than BALB/c mice. In vitro, BCG-infected bone marrow derived macrophages (BMM) from both mouse strains displayed similar capacities to either phagocytose bacteria or produce soluble mediators such as TNF, IL-12 and nitric oxide (NO). Although IFN-gamma stimulation of infected BMM in both mouse strains resulted in the induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The above observations indicate that the chain of early, possibly innate immunological events occurring during pulmonary mycobacterial infection may directly impact on increased susceptibility or resistance to infection.

  • 7. Askling, H. H.
    et al.
    Vene, S.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centrum för klinisk forskning i D län (CKFD).
    Lindquist, L.
    Immunogenicity of delayed TBE-vaccine booster2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 3, p. 499-502Article in journal (Refereed)
    Abstract [en]

    Information is scarce regarding the antibody response when TBE-vaccine booster doses are delayed, which is a common situation in daily life. We have investigated the immune response after a delayed booster dose compared to a normal booster interval in an every-day setting. Overall, 250/260 (96%) of the study participants had neutralizing antibodies post-booster, with no significant difference between normal and delayed booster intervals. Based on our findings we propose that healthy individuals who have failed adherence to the recommended schedule of TBE-vaccination can be given a delayed dose without concern of immunogenicity.

  • 8. Balogun, H. A.
    et al.
    Vasconcelos, N. -M
    Lindberg, Robert
    Södertörn University, School of Life Sciences.
    Haeggström, M.
    Moll, K.
    Chen, Q.
    Wahlgren, M.
    Berzins, K.
    Immunogenicity and antigenic properties of Pf332-C231, a fragment of a non-repeat region of the Plasmodium falciparum antigen Pf3322009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 1, p. 90-97Article in journal (Refereed)
    Abstract [en]

    Antigen Pf332, a megadalton protein has been shown to be associated with the membrane of infected erythrocytes Detailed functional studies on the antigen have remained hampered by the cross-reactive nature of antibodies generated to Pf332 PB32-C231, identified in the C-terminal region of Pf332 was cloned and antibodies against the C231 fragment were shown to react with intact Pf332 antigen by both immunofluorescence and immunoblotting analyses Antibodies to C231 inhibited in vitro Plasmodium falciparum growth efficiently In addition. human sera from malaria-exposed individuals reacted with recombinant C231 We show that Pf332-C231 represents a functional domain and is expected to facilitate further studies on Pf332 as a potential target for protective immune responses and the function of the antigen.

  • 9.
    Balogun, Halima A.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Awah, Nancy W.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Farouk, Salah E.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pf332-C231-reactive antibodies affect growth and development of intra-erythrocytic Plasmodium falciparum parasites2011In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    The Plasmodium falciparum antigen 332 (Pf332), is a megadalton parasite protein expressed at the surface of infected red cells during later stages of the parasite's developmental cycle. Antibodies to different parts of this antigen have been shown to inhibit parasite growth and adherence to host cells with or without ancillary cells. However, the mechanisms involved in these inhibitions remain largely unknown. We further analysed the activities of specific antibodies with regard to their specific mechanisms of action. For these analyses, affinity purified human antibodies against epitopes in the C-terminal fragment of Pf332 (Pf332-C231) were employed. All purified antibodies recognized Pf332-C231 both by immunofluorescence and ELISA. IgG was the main antibody isotype detected, although all sera investigated had varying proportions of IgG and IgM content. All the antibodies showed a capacity to inhibit parasite growth in P. falciparum cultures to different extents, mainly by acting on the more mature parasite stages. Morphological analysis revealed the antibody effects to be characterized by the presence of a high proportion of abnormal schizonts (15-30%) and pyknotic parasites. There was also an apparent antibody effect on the red cell integrity, as many developing parasites (up to 10% of trophozoites and schizonts) were extracellular. In some cases, the infected red cells appeared to be disintegrating/fading, staining paler than surrounding infected and uninfected cells. Antigen reversal of inhibition confirmed that these inhibitions were antigen specific. Furthermore, the growth of parasites after 22-42 h exposure to antibodies was investigated. Following the removal of antibody pressure, a decreased growth rate of these parasites was seen compared to that of control parasites. The present study confirms the potential of Pf332 as a target antigen for parasite neutralizing antibodies, and further indicates that epitopes within the C231 region of Pf332 should constitute important tools in the dissection of the role of Pf332 in the biology of the malaria parasite, as well as in the design of a malaria vaccine.

  • 10.
    Balogun, Halima A.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Vasconcelos, N.-M.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Lindberg, R.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Haeggström, M.
    Moll, K.
    Chen, Q.
    Wahlgren, M.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Immunogenicity and antigenic properties of Pf332-C231, a fragment of a non-repeat region of the Plasmodium falciparum antigen Pf332 2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 1, p. 90-97Article in journal (Refereed)
    Abstract [en]

    Antigen Pf332, a megadalton protein has been shown to be associated with the membrane of infected erythrocytes. Detailed functional studies on the antigen have remained hampered by the cross-reactive nature of antibodies generated to Pf332. Pf332-C231, identified in the C-terminal region of Pf332 was cloned and antibodies against the C231 fragment were shown to react with intact Pf332 antigen by both immunofluorescence and immunoblotting analyses. Antibodies to C231 inhibited in vitro Plasmodium falciparum growth efficiently. In addition, human sera from malaria-exposed individuals reacted with recombinant C231. We show that Pf332-C231 represents a functional domain and is expected to facilitate further studies on Pf332 as a potential target for protective immune responses and the function of the antigen.

  • 11.
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Diverse microbial exposure: Consequences for vaccine development2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 29, p. 4336-4340Article, review/survey (Refereed)
    Abstract [en]

    Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.

  • 12. Blom, Hans
    et al.
    Bennemo, Mia
    Berg, Mikael
    Lemmens, Raf
    Flocculate removal after alkaline lysis in plasmid DNA production.2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 29, no 1, p. 6-10Article in journal (Refereed)
    Abstract [en]

    Alkaline lysis is the most commonly used method following harvest of bacterial cells for production of plasmid DNA. The method was originally developed for laboratory scale experiments and has shown to be challenging at larger scales. A major problem prior to further downstream processing is the risk of filter clogging without efficient removal of the flocculate that occurs after neutralization. For this purpose we here present a scalable method where the clarification of alkaline lysate is greatly simplified. Through a rapid procedure, involving the addition of ammonium hydrogen carbonate to the neutralized alkaline lysate, the flocculate is lifted to the surface of the solution by the released carbon dioxide and ammonium. After this step a clarified solution can be drained from the bottom of the vessel. The procedure does not impact pH, plasmid DNA concentration or the ratio of open circular to supercoiled plasmid DNA in the solution.

  • 13.
    Bråve, Andreas
    et al.
    Swedish Institute for Infectious Disease Control & Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Sweden .
    Johansen, Kari
    Swedish Institute for Infectious Disease Control & Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Sweden .
    Palma, Paolo
    Division of Immunology and Infectious Diseases, Ospedale Pediatrico Bambino Gesù and Chair of Paediatrics, Department of Public Health, University of Rome Tor Vergata, Italy .
    Benthin, Reinhold
    Swedish Institute for Infectious Disease Control & Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Sweden .
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Maternal immune status influences HIV-specific immune responses in pups after DNA prime protein boost using mucosal adjuvant2008In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 47, p. 5957-5966Article in journal (Refereed)
    Abstract [en]

    This study was designed to determine the impact of maternal HIV-1 specific immunity on HIV-DNA immunization of 2 weeks old pups during the breast-feeding period.

    Adult female mice received intranasal or intradermal HIV DNA (gp160Env, p37Gag, Nef, Tat and Rev) prime and recombinant protein booster immunizations that induced mucosal and systemic HIV-1 specific B and T cell responses. Intranasal administration of the immunogens induced higher serum IgG titers to HIV antigens than the intradermal immunization. Furthermore, predominantly higher HIV-1 specific fecal IgA titers were obtained in nasally immunized mice. The capacity to respond to one single prime with DNA and one boost with recombinant protein was then compared in pups born to mothers displaying HIV-1-specific immune responses and in pups born to non-vaccinated mothers. Immune responses to the greatest number of antigens were detected in pups born to mothers having the highest HIV-1 specific immune responses. These data suggest that HIV-1 DNA-plasmid immunization during breast-feeding and recombinant protein boosting shortly thereafter enhances the breadth of the humoral HIV-1 specific immune responses.

  • 14. Bråve, Andreas
    et al.
    Hallengärd, David
    Schröder, Ulf
    Blomberg, Pontus
    Wahren, Britta
    Hinkula, Jorma
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses2008In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 40, p. 5075-5078Article in journal (Refereed)
    Abstract [en]

    One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity. © 2008 Elsevier Ltd. All rights reserved.

  • 15. Bucht, Göran
    et al.
    Sjölander, Katarina Brus
    Eriksson, Solveig
    Lindgren, Lena
    Lundkvist, Åke
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Modifying the cellular transport of DNA-based vaccines alters the immune response to hantavirus nucleocapsid protein2001In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 19, no 28-29, p. 3820-3829Article in journal (Refereed)
    Abstract [en]

    Puumala virus is a member of the hantavirus genus (family Bunyaviridae) and is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS) in Europe. A genetic vaccination approach was conducted to investigate if the immune response could be modulated using different cellular secretion and/or localisation signals, and the immune responses were analysed in BALB/c mice and in a bank vole infectious model. Rodents vaccinated with DNA constructs encoding the antigen fused to an amino-terminal secretion signal raised significantly higher antibody levels when compared to using constructs lacking secretion signals. Furthermore, the ratios of the IgG subclasses (IgG2a/IgG1) were raised by the use of cellular localisation signals, indicating a more pronounced Th1-type of immune response. The majority of the mice, or bank voles, immunised with DNA encoding a secreted form of the antigen showed a positive lymphoproliferative response and were protected against challenge with Puumala virus (strain Kazan-wt).

  • 16.
    Buonaguro, L
    et al.
    Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy.
    Devito, C
    Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Tornesello, ML
    Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy.
    Schröder, U
    Eurocine Vaccines AB, Sweden.
    Wahren, B
    Karolinska Institute, Sweden.
    Hinkula, Jorma
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    Buonaguro, FM
    Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy.
    DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity2007In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 25, no 32, p. 5968-5977Article in journal (Refereed)
    Abstract [en]

    The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3. © 2007 Elsevier Ltd. All rights reserved.

  • 17. Cano, F.
    et al.
    Plotnicky-Gilquin, H.
    Nguyen, T. N.
    Liljeqvist, S.
    Samuelson, Patrik
    KTH, Superseded Departments, Biotechnology.
    Bonnefoy, J. Y.
    Ståhl, Stefan
    KTH, Superseded Departments, Biotechnology.
    Robert, A.
    Partial protection to respiratory syncytial virus (RSV) elicited in mice by intranasal immunization using live staphylococci with surface-displayed RSV-peptides2000In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 18, no 24, p. 2743-2752Article in journal (Refereed)
    Abstract [en]

    A live bacterial vaccine-delivery system based on the food-grade bacterium Staphylococcus carnosus was used for delivery of peptides from the G glycoprotein of human respiratory syncytial virus, subtype A (RSV-A). Three peptides, corresponding to the G protein amino acids, 144-159 (denoted G5), 190-203 (G9) and 171-188 (G4 S), the latter with four cysteine residues substituted for serines, were expressed by recombinant means as surface-exposed on three different bacteria, and their surface accessibility on the bacteria was verified by fluorescence-activated cell sorting (FACS). Intranasal immunization of mice with the live recombinant staphylococci elicited significant anti-peptide as well as anti-virus serum IgG responses of balanced IgG1/IgG2a isotype profiles, and upon viral challenge with 10(5) tissue culture infectious doses(50) (TCID50), lung protection was demonstrated for approximately half of the mice in the G9 and G4 S immunization groups. To our knowledge, this is the first study in which protective immunity to a viral pathogen has been evoked using food-grade bacteria as vaccine-delivery vehicles.

  • 18.
    Carlsson, R. M.
    et al.
    Public Health Agency Sweden, Sweden; Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Gustafsson, L.
    Public Health Agency Sweden, Sweden.
    Hallander, H. O.
    Public Health Agency Sweden, Sweden.
    Ljungman, M.
    Public Health Agency Sweden, Sweden.
    Olin, P.
    Public Health Agency Sweden, Sweden.
    Gothefors, L.
    Public Health Agency Sweden, Sweden; Umeå University, Sweden.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Allergy Center. Linköping University, Faculty of Medicine and Health Sciences. Public Health Agency Sweden, Sweden.
    Netterlid, E.
    Public Health Agency Sweden, Sweden; Lund University, Sweden; Skåne University Hospital, Sweden.
    Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years2015In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 33, no 31, p. 3717-3725Article in journal (Refereed)
    Abstract [en]

    Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 mu g) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 mu g). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. (C) 2015 Elsevier Ltd. All rights reserved.

  • 19.
    Carlsson, R. M.
    et al.
    Göteborg, Sweden; Public Health Agency of Sweden, Sweden.
    Gustafsson, L.
    Public Health Agency of Sweden, Sweden.
    Hallander, H. O.
    Public Health Agency of Sweden, Sweden.
    Ljungman, M.
    Public Health Agency of Sweden, Sweden.
    Olin, P.
    Public Health Agency of Sweden, Sweden.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Public Health Agency of Sweden, Sweden.
    Nilsson, L.
    Public Health Agency of Sweden, Sweden; Linköping, Sweden.
    Netterlid, E.
    Public Health Agency of Sweden, Sweden; Malmö, Sweden.
    Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years2015In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 33, no 31, p. 3717-3725Article in journal (Refereed)
    Abstract [en]

    Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 mu g) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 mu g). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. (C) 2015 Elsevier Ltd. All rights reserved.

  • 20.
    Chlibek, Roman
    et al.
    Univ Def, Fac Mil Hlth Sci, Hradec Kralove, Czech Republic..
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    van Rijckevorsel, Gini
    Publ Hlth Serv Amsterdam, Dept Infect Dis, Amsterdam, Netherlands..
    Richardus, Jan H.
    Municipal Publ Hlth Serv Rotterdam Rijnmond, Rotterdam, Netherlands..
    Plassmann, Georg
    Unterfrintroper Hausarztzentrum, Essen, Germany..
    Schwarz, Tino F.
    Stiftung juliusspital, Cent Lab, Wurzburg, Germany.;Stiftung juliusspital, Vaccinat Ctr, Wurzburg, Germany..
    Catteau, Gregory
    GSK Vaccines, Wavre, Belgium..
    Lal, Himal
    GSK Vaccines, King Of Prussia, PA USA..
    Heineman, Thomas C.
    GSK Vaccines, King Of Prussia, PA USA..
    Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults2016In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 34, no 6, p. 863-868Article in journal (Refereed)
    Abstract [en]

    Background: An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01(B) adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25 mu g, 50 mu g, or 100 mu g gE) was conducted in adults >= 60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50 mu g gE/AS01(B) formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination. Methods: This phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4(+) T cells expressing >= 2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose. Results: Six years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20-25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3 mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72. Conclusions: gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.

  • 21. Chlibek, Roman
    et al.
    Smetana, Jan
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rombo, Lars
    Van den Hoek, J. Anneke R.
    Richardus, Jan H.
    Plassmann, Georg
    Schwarz, Tino F.
    Ledent, Edouard
    Heineman, Thomas C.
    Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: A phase II, randomized, controlled study2014In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, no 15, p. 1745-1753Article in journal (Refereed)
    Abstract [en]

    Background: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system ASO1(B). Methods: In this phase II, single-blind, randomized, controlled study, adults aged >= 60 years (N = 714) received one dose of 100 mu g gE/AS01(B), two doses, two months apart, of 25, 50, or 100 mu g gE/AS01(B), or two doses of unadjuvanted 100 mu g gE/saline. Frequencies of CD4(+) T cells expressing >= 2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. Results: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01(B) formulations than after one dose of 100 mu g gE/AS01(B) or two doses of 100 mu g gE/saline. Frequencies were comparable after two doses of 25, 50, or 100 mu g gE/AS01g. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100 mu g gE/AS01(B) and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01(B) formulations were similar but greater than with gE/saline. Conclusions: The three formulations of gE/AS01(B) were immunogenic and well tolerated in adults aged >= 60 years. Two vaccinations with gE/AS01(B) induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).

  • 22.
    Clarke, S. C.
    et al.
    Scottish Meningococcus and Pneumococcus Reference Laboratory, North Glasgow University Hospitals NHS Trust, Stobhill Hospital, Scotland, UK and Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
    Diggle, M. A.
    Scottish Meningococcus and Pneumococcus Reference Laboratory, North Glasgow University Hospitals NHS Trust, Stobhill Hospital, Scotland, UK.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Analysis of PorA variable region 3 in meningococci: implications for vaccine policy?2003In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 21, no 19-20, p. 2468-2473Article in journal (Refereed)
    Abstract [en]

    Outer membrane protein (OMP) vaccines are being developed against Neisseria meningitidis serogroup B which may provide protection against common circulating serotypes and serosubtypes in some countries. However, limited data is available in Europe from genosubtyping meningococci. We therefore undertook a retrospective analysis of the three main variable regions, VR1, VR2 as well as VR3, of the porA gene from N. meningitidis isolated from different countries, mainly from Scotland and Sweden. Analysis of this gene showed that, amongst 226 strains studied, there were a total of 78 different strains. No new VR1 or VR2 alleles were found but five new VR3 alleles are described. Our data indicates the importance of analysing the VR3 region of PorA in addition to VR1 and VR2 and also highlights, in general terms, the need for genosubtyping meningococci. Such analyses have major implications for the design of new meningococcal vaccines.

  • 23.
    Conlan, J Wayne
    et al.
    NRC, Kanada.
    Shen, Hua
    Golovliov, Igor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Zingmark, Carl
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Oyston, Petra CF
    Chen, Wangxue
    House, Robert V
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Differential ability of novel attenuated targeted deletion mutants of Francisella tularensis subspecies tularensis strain SCHU S4 to protect mice against aerosol challenge with virulent bacteria: effects of host background and route of immunization2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 7, p. 1824-1831Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis subspecies tularensis is a highly virulent facultative intracellular pathogen of humans and a potential biological weapon. A live vaccine strain, F. tularensis LVS, was developed more than 50 years ago by pragmatic attenuation of a strain of the less virulent holarctica subspecies. LVS was demonstrated to be highly effective in human volunteers who were exposed to intradermal challenge with fully virulent subsp. tularensis, but was less effective against aerosol exposure. LVS faces regulatory hurdles that to date have prevented its licensure for general use. Therefore, a better defined and more effective vaccine is being sought. To this end we have created gene deletion mutants in the virulent subsp. tularensis strain and tested them for their ability to elicit a protective immune response against systemic or aerosol challenge with the highly virulent wild-type subsp. tularensis strain, SCHU S4. Both oral and intradermal (ID) primary vaccination routes were assessed in BALB/c and C3H/HeN mice as was oral boosting. One SCHU S4 mutant missing the heat shock gene, clpB, was significantly more attenuated than LVS whereas a double deletion mutant missing genes FTT0918 and capB was as attenuated as LVS. In general mice immunized with SCHU S4DeltaclpB were significantly better protected against aerosol challenge than mice immunized with LVS. A single ID immunization of BALB/c mice with SCHU S4DeltaclpB was at least as effective as any other regimen examined. Mice immunized with SCHU S4Delta0918DeltacapB were generally protected to a similar degree as mice immunized with LVS. A preliminary examination of immune responses to vaccination with LVS, SCHU S4DeltaclpB, or SCHU S4Delta0918DeltacapB provided no obvious correlate to their relative efficacies.

  • 24. Cordonnier, Catherine
    et al.
    Labopin, Myriam
    Chesnel, Virginie
    Ribaud, Patricia
    De La Camara, Rafael
    Martino, Rodrigo
    Ullmann, Andrew J.
    Parkkali, Terttu
    Locasciulli, Anna
    Yakouben, Karima
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Bonnet, Eric
    Einsele, Hermann
    Niederwieser, Dietger
    Apperley, Jane
    Ljungman, Per
    Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients: Results from the EBMT IDWP01 trial2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 15, p. 2730-2734Article in journal (Refereed)
    Abstract [en]

    The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (>= 0.15 mu g/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant. (C) 2010 Elsevier Ltd. All rights reserved.

  • 25.
    Dannetun, Eva
    et al.
    Smittskyddsenheten US.
    Tegnell, Anders
    Dept of Epidemiology Smittskyddsinstitutet, Solna.
    Hermansson, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Törner, Anna
    Avd för Epidemiologi Smittskyddsinstitutet, Solna.
    Giesecke, Johan
    Avd för Epidemiologi Smittskyddsinstitutet, Solna.
    Timeliness of MMR vaccination - Influence on vaccination coverage2004In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 22, no 31-32, p. 4228-4232Article in journal (Refereed)
    Abstract [en]

    Over the last seven years, and especially in 2001, a declining coverage for MMR vaccination in 2-year-olds has been noted in Sweden. By recording actual date of vaccination in a cohort of almost 4000 children in a county in central Sweden, we found that parents' decision to postpone vaccination by up to 1.5 years beyond the stipulated age of 18 months accounted for about half the reported drop in 2001. Even if coverage thus improves with time, postponed vaccination adds to the pool of unprotected children in the population. The design of the current national surveillance system overestimates coverage at 2 years and fails to record delayed vaccination. To avoid future outbreaks that can appear around imported cases of measles it is crucial to attain high coverage levels by timely vaccination. © 2004 Elsevier Ltd. All rights reserved.

  • 26.
    de Bekker-Grob, Esther W.
    et al.
    Erasmus Univ, Sect Hlth Technol Assessment, POB 1738, NL-3000 DR Rotterdam, Netherlands.;Erasmus Univ, Inst Hlth Policy & Management, Erasmus Choice Modelling Ctr, Rotterdam, Netherlands.;Erasmus MC Univ Med Ctr, Sect Med Decis Making, Rotterdam, Netherlands.;Erasmus MC Univ Med Ctr, Dept Publ Hlth, Erasmus Choice Modelling Ctr, Rotterdam, Netherlands..
    Veldwijk, Jorien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics. Erasmus Univ, Sect Hlth Technol Assessment, POB 1738, NL-3000 DR Rotterdam, Netherlands.;Erasmus Univ, Inst Hlth Policy & Management, Erasmus Choice Modelling Ctr, Rotterdam, Netherlands.
    Jonker, Marcel
    Erasmus Univ, Sect Hlth Technol Assessment, POB 1738, NL-3000 DR Rotterdam, Netherlands.;Erasmus Univ, Inst Hlth Policy & Management, Erasmus Choice Modelling Ctr, Rotterdam, Netherlands..
    Donkers, Bas
    Erasmus Univ, Dept Business Econ, Rotterdam, Netherlands.;Erasmus Univ, Erasmus Sch Econ, Erasmus Choice Modelling Ctr, Rotterdam, Netherlands..
    Huisman, Jan
    Het Doktershuis, Ridderkerk, Netherlands..
    Buis, Sylvia
    Gezondheidsctr Ommoord, Rotterdam, Netherlands..
    Swait, Joffre
    Univ South Australia, Inst Choice, Sydney, NSW, Australia..
    Lancsar, Emily
    Monash Univ, Ctr Hlth Econ, Melbourne, Vic, Australia..
    Witteman, Cilia L. M.
    Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands..
    Bonsel, Gouke
    EuroQol Fdn, Rotterdam, Netherlands..
    Bindels, Patrick
    Erasmus MC Univ Med Ctr, Dept Gen Practice, Rotterdam, Netherlands..
    The impact of vaccination and patient characteristics on influenza vaccination uptake of elderly people: A discrete choice experiment2018In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 36, no 11, p. 1467-1476Article in journal (Refereed)
    Abstract [en]

    Objectives: To improve information for patients and to facilitate a vaccination coverage that is in line with the EU and World Health Organization goals, we aimed to quantify how vaccination and patient characteristics impact on influenza vaccination uptake of elderly people.

    Methods: An online discrete choice experiment (DCE) was conducted among 1261 representatives of the Dutch general population aged 60 years or older. In the DCE, we used influenza vaccination scenarios based on five vaccination characteristics: effectiveness, risk of severe side effects, risk of mild side effects, protection duration, and absorption time. A heteroscedastic multinomial logit model was used, taking scale and preference heterogeneity (based on 19 patient characteristics) into account.

    Results: Vaccination and patient characteristics both contributed to explain influenza vaccination uptake. Assuming a base case respondent and a realistic vaccination scenario, the predicted uptake was 58%. One-way changes in vaccination characteristics and patient characteristics changed this uptake from 46% up to 61% and from 37% up to 95%, respectively. The strongest impact on vaccination uptake was whether the patient had been vaccinated last year, whether s/he had experienced vaccination side effects, and the patient's general attitude towards vaccination.

    Conclusions: Although vaccination characteristics proved to influence influenza vaccination uptake, certain patient characteristics had an even higher impact on influenza vaccination uptake. Policy makers and general practitioners can use these insights to improve their communication plans and information regarding influenza vaccination for individuals aged 60 years or older. For instance, physicians should focus more on patients who had experienced side effects due to vaccination in the past, and policy makers should tailor the standard information folder to patients who had been vaccinated last year and to patient who had not.

  • 27. de Sandt, Carolien E. van
    et al.
    Kreijtz, Joost H. C. M.
    Geelhoed-Mieras, Martina M.
    Vogelzang-van Trierum, Stella E.
    Nieuwkoop, Nella J.
    van de Vijver, David A. M. C.
    Fouchier, Ron A. M.
    Osterhaus, Albert D. M. E.
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rimmelzwaan, Guus F.
    Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine2014In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, no 43, p. 5614-5623Article in journal (Refereed)
    Abstract [en]

    Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus-specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT-adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8(+) T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses.

  • 28. de Villiers, Sabina H. L.
    et al.
    Lindblom, Nina
    Kalayanov, Genadiy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Gordon, Sandra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Baraznenok, Ivan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Malmerfelt, Anna
    Marcus, Monica M.
    Johansson, Anette M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Svensson, Torgny H.
    Nicotine hapten structure, antibody selectivity and effect relationships: Results from a nicotine vaccine screening procedure2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 10, p. 2161-2168Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to synthesise and screen a set of novel nicotine hapten immunogens used for the treatment of nicotine dependence. In the screening process we studied the amount of antibodies generated and their selectivity, using ELISA techniques, and their effects on nicotine-induced dopamine release in the NAC(shell) of the rat, assessed by in vivo voltammetry. We conclude that even small changes such as the linker attachment on the nicotine molecule as well as the structure of the linker may greatly influence the selectivity of the antibodies and the central neurobiological effects of nicotine that are considered critical for its dependence producing properties. (C) 2010 Elsevier Ltd. All rights reserved.

  • 29.
    Eilers, R.
    et al.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30-001, NL-9700 RB Groningen, Netherlands.;Natl Inst Publ Hlth & Environm RIVM, Ctr Infect Dis Control, POB 1, NL-3720 BA Bilthoven, Netherlands..
    de Melker, H. E.
    Natl Inst Publ Hlth & Environm RIVM, Ctr Infect Dis Control, POB 1, NL-3720 BA Bilthoven, Netherlands..
    Veldwijk, Jorien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics. Natl Inst Publ Hlth & Environm RIVM, Ctr Nutr Prevent & Hlth Serv, NL-3720 BA Bilthoven, Netherlands.
    Krabbe, P. F. M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30-001, NL-9700 RB Groningen, Netherlands..
    Vaccine preferences and acceptance of older adults2017In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, no 21, p. 2823-2830Article in journal (Refereed)
    Abstract [en]

    Background: Expanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination.

    Methods: A discrete choice experiment was conducted to generate choice data that was analyzed using a mixed multinomial logit statistical model.

    Results: Important factors that were associated with vaccination acceptance in older adults are high mortality risk of the infectious disease, high susceptibility of getting the infectious disease, and high vaccine effectiveness. Age, influenza vaccination in 2013 and self-perceived health score were identified as personal factors that affect vaccine preference. Potential vaccination rates of older adults were estimated at 68.1% for pneumococcal vaccination, 58.1% for herpes zoster vaccination, 53.9% for pertussis vaccination and 54.3% for influenza vaccination. For persons aged 50-65, potential vaccination rates were estimated at 58.1% for pneumococcal vaccination, 49.5% for herpes zoster vaccination, 43.9% for pertussis vaccination and 42.2% for influenza vaccination. For persons aged 65 and older, these were respectively 76.2%, 67.5%, 57.5% and 65.5%.

    Discussion: Our results suggest that older adults are most likely to accept pneumococcal vaccination of the four vaccines. Information provision accompanied with the implementation of a new vaccine has to be tailored for the individual and the vaccine it concerns. Special attention is needed to ensure high uptake among persons aged 50-65 years.

  • 30.
    Elias, D.
    et al.
    Microbiol. and Tumor Biology Center, Karolinska Institute, Box 280, 17177 Stockholm, Sweden, Swed. Inst. for Infect. Dis. Contr., Stockholm, Sweden, Armauer Hansen Research Institute, Box 1005, Addis Ababa, Ethiopia.
    Akuffo, H.
    Microbiol. and Tumor Biology Center, Karolinska Institute, Box 280, 17177 Stockholm, Sweden.
    Pawlowski, A.
    Swed. Inst. for Infect. Dis. Contr., Stockholm, Sweden.
    Haile, M.
    Swed. Inst. for Infect. Dis. Contr., Stockholm, Sweden.
    Schön, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology .
    Britton, S.
    Department of Medicine, Unit of Infectious Diseases, Karolinska Institute, 17176 Stockholm, Sweden.
    Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis2005In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 23, no 11, p. 1326-1334Article in journal (Refereed)
    Abstract [en]

    We hypothesized that the ability of BCG vaccination to protect against Mycobacterium tuberculosis is less in hosts exposed to chronic helminthes infection compared to unexposed individuals. To test this hypothesis we evaluated the efficacy of BCG vaccination in protecting against M. tuberculosis challenge in Schistosoma mansoni pre-infected mice by analyzing their ability to limit the replication of TB bacilli in the lung and liver and the histology of lung sections. The results show that BCG vaccinated mice with prior S. mansoni infection show significantly higher number of colony forming units of TB bacilli as well as significant reduction in air exchange area in the lung compared to controls. In addition, spleen cells from S. mansoni infected mice were found to produce significantly less IFN-? and nitric oxide when stimulated in vitro with PPD and several fold higher soluble egg antigen (SEA) and Concanavalin A induced IL-4 and IL-5 secretion. Taken together, our data show that S. mansoni infection reduces the protective efficacy of BCG vaccination against M. tuberculosis possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile. © 2004 Published by Elsevier Ltd.

  • 31.
    Ellström, Patrik
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Latorre-Margalef, Neus
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Griekspoor, Petra
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Waldenström, Jonas
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Olofsson, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Wahlgren, John
    Ctr Microbiol Preparedness KCB, Swedish Inst Infect Dis Control SMI, SE-17182 Solna, Sweden.
    Olsen, Björn
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Sampling for low-pathogenic avian influenza A virus in wild Mallard ducks: Oropharyngeal versus cloacal swabbing2008In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 35, p. 4414-4416Article in journal (Refereed)
  • 32. Ellström, Patrik
    et al.
    Latorre-Margalef, Neus
    Griekspoor, Petra
    Waldenström, Jonas
    Olofsson, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Wahlgren, John
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Sampling for low-pathogenic avian influenza A virus in wild Mallard ducks: oropharyngeal versus cloacal swabbing2008In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 35, p. 4414-4416Article in journal (Refereed)
  • 33.
    Eriksson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Tötterman, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Maltais, Anna-Karin
    Pisa, Pavel
    Yachnin, Jeffrey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, no 37, p. 3843-3848Article in journal (Refereed)
    Abstract [en]

    We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment. Vaccine doses ranged from 50 to 1600 mu g. Study subjects received five vaccinations at four week intervals. All patients have had at least one year of follow-up. No systemic toxicity was observed. Discomfort from electroporation did not require analgesia or topical anesthetic. No clinically significant changes in PSA kinetics were observed as all patients required antiandrogen therapy shortly after completion of the 5 months of vaccination due to rising PSA. Immunogenicity, as measured by T-cell reactivity to the modified PSA peptide and to a mix of overlapping PSA peptides representing the full length protein, was observed in some patients. All but one patient had pre-study PSA specific T-cell reactivity. ADT alone resulted in increases in T-cell reactivity in most patients. Intradermal vaccination with skin electroporation is easily performed with only minor discomfort for the patient. Patients with biochemical relapse of prostate cancer are a good model for testing immune therapies.

  • 34. Erra, Elina O.
    et al.
    Askling, Helena Hervius
    Yoksan, Sutee
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Riutta, Jukka
    Vene, Sirkka
    Lindquist, Lars
    Vapalahti, Olli
    Kantele, Anu
    Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis: A two-year follow-up study2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, no 1, p. 119-123Article in journal (Refereed)
    Abstract [en]

    Background:

    The inactivated Vero cell-derived vaccine (JE-VC, IXIARO) has replaced the traditional mouse brain-derived preparations (JE-MB) in travelers' vaccinations against Japanese encephalitis. We showed recently that a single JE-VC dose efficiently boosts immunity in JE-MB-primed vaccinees, and that JE-VC elicits cross-protective immunity against non-vaccine genotypes, including the emerging genotype I. While these studies only provided short-term data, the present investigation evaluates the longevity of seroprotection in the same volunteers.

    Methods:

    The study comprised 48 travelers who had received (1) JE-VC primary series, (2) JE-MB primary series followed by a single JE-VC booster dose, or (3) JE-MB primary series and a single JE-MB booster dose. Serum samples were collected two years after the last vaccine dose, and evaluated with the plaque-reduction neutralization test against seven Japanese encephalitis virus strains representing genotypes I-IV. PRNT50 titers >= 10 were considered protective.

    Results:

    Two years after the primary series with JE-VC, 87-93% of the vaccinees proved to be cross-protected against test strains representing genotypes II-IV and 73% against those of genotype I. After a single homologous or heterologous booster dose to JE-MB-primed subjects, the two-year seroprotection rates against genotype I-IV strains were 89-100%.

    Conclusions:

    After JE-VC primary series, seroprotection appeared to wane first against genotype I. The first booster should not be delayed beyond two years. In JE-MB-primed subjects, a single JE-VC booster provided cross-protective immunity against genotype I-IV strains in almost all vaccinees, suggesting an interval of two years or even longer for the second booster. These data further support the use of a single JE-VC dose for boosting JE-MB immunity.

  • 35.
    Fernando, Germain J. P.
    et al.
    Vaxxas Pty Ltd, Australia.
    Hickling, Julian
    Working Tandem Ltd, England.
    Flores, Cesar M. Jayashi
    Vaxxas Pty Ltd, Australia.
    Griffin, Paul
    QIMR Berghofer Med Res Inst, Australia; Q Pharm Pry Ltd, Australia; Mater Hosp, Australia; Mater Res Inst, Australia; Univ Queensland, Australia.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Skinner, S. Rachel
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Davies, Cristyn
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Witham, Katey
    Vaxxas Pty Ltd, Australia.
    Pryor, Melinda
    360Biolabs Pry Ltd, Australia.
    Bodle, Jesse
    Seqirus Pty Ltd, Australia.
    Rockman, Steve
    Seqirus Pty Ltd, Australia; Univ Melbourne, Australia.
    Frazer, Ian H.
    Not Found:[Fernando, Germain J. P.; Flores, Cesar M. Jayashi; Witham, Katey; Forster, Angus H.] Vaxxas Pty Ltd, Translat Res Inst, 37 Kent St, Brisbane, Qld 4102, Australia; [Hickling, Julian] Working Tandem Ltd, Cambridge, England; [Griffin, Paul] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia; [Griffin, Paul] Q Pharm Pry Ltd, Brisbane, Qld, Australia; [Griffin, Paul] Mater Hosp, Dept Med and Infect Dieases, Brisbane, Qld, Australia; [Griffin, Paul] Mater Res Inst, Brisbane, Qld, Australia; [Griffin, Paul] Univ Queensland, Brisbane, Qld, Australia; [Anderson, Christopher D.] Linkoping Univ, Dept Clin and Expt Med, Fac Hlth Sci, Linkoping, Sweden; [Anderson, Christopher D.] Heart and Med Ctr, Dept Dermatol and Venereol, Region Ostergotland, Sweden; [Skinner, S. Rachel; Davies, Cristyn] Univ Sydney, Sydney Med Sch, Discipline Child and Adolescent Hlth, Sydney, NSW, Australia; [Skinner, S. Rachel; Davies, Cristyn] Childrens Hosp Westmead, Sydney, NSW, Australia; [Pryor, Melinda] 360Biolabs Pry Ltd, Burnet Inst, Melbourne, Vic, Australia; [Bodle, Jesse; Rockman, Steve] Seqirus Pty Ltd, Melbourne, Vic, Australia; [Rockman, Steve] Univ Melbourne, Melbourne, Vic, Australia;.
    Forster, Angus H.
    Vaxxas Pty Ltd, Australia.
    Safety, tolerability, acceptability and immunogenicity of an influenza vaccine delivered to human skin by a novel high-density microprojection array patch (Nanopatch (TM))2018In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 36, no 26, p. 3779-3788Article in journal (Refereed)
    Abstract [en]

    Background: Injection using needle and syringe (Namp;S) is the most widely used method for vaccination, but requires trained healthcare workers. Fear of needles, risk of needle-stick injury, and the need to reconstitute lyophilised vaccines, are also drawbacks. The Nanopatch (NP) is a microarray skin patch comprised of a high-density array of microprojections dry-coated with vaccine that is being developed to address these shortcomings. Here we report a randomised, partly-blinded, placebo-controlled trial that represents the first use in humans of the NP to deliver a vaccine. Methods: Healthy volunteers were vaccinated once with one of the following: (1) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 mu g haemagglutinin (HA) per dose), applied to the volar forearm (NP-HAIFA), n = 15; (2) NPs coated with split inactivated influenza virus (A/California/07/2009 11-11N1 I, 15 mu g HA per dose), applied to the upper arm (NP-HA/UA), n = 15; (3) Fluvaxe (R) 2016 containing 15 mu g of the same H1N1 HA antigen injected intramuscularly (IM) into the deltoid (IM-HA/D), n = 15; (4) NPs coated with excipients only, applied to the volar forearm (NP-placebo/FA), n = 5; (5) NPs coated with excipients only applied to the upper arm (NP-placebo/UA), n = 5; or (6) Saline injected IM into the deltoid (IM-placebo/D), n = 5. Antibody responses at days 0, 7, and 21 were measured by haemagglutination inhibition (HAI) and microneutralisation (MN) assays. Findings: NP vaccination was safe and acceptable; all adverse events were mild or moderate. Most subjects (55%) receiving patch vaccinations (HA or placebo) preferred the NP compared with their past experience of IM injection with Namp;S (preferred by 24%). The antigen-vaccinated groups had statistically higher HAI titres at day 7 and 21 compared with baseline (p amp;lt; 0.0001), with no statistical differences between the treatment groups (p amp;gt; 0.05), although the group sizes were small. The geometric mean HAI titres at day 21 for the NP-HA/FA, NP-HA/UA and IM-HA/D groups were: 335 (189-593 95% CI), 160 (74-345 95% CI), and 221 (129-380 95% CI) respectively. A similar pattern of responses was seen with the MN assays. Application site reactions were mild or moderate, and more marked with the influenza vaccine NPs than with the placebo or IM injection. Interpretation: Influenza vaccination using the NP appeared to be safe, and acceptable in this first time in humans study, and induced similar immune responses to vaccination by IM injection. (C) 2018 The Author(s). Published by Elsevier Ltd.

  • 36. Fierabracci, A
    et al.
    Biro, PA
    Yiangou, Y
    Mennuni, C
    Luzzago, A
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Cortese, R
    Bottazzo, GF
    Osteopontin is an autoantigen of the somatostatin cells in human islets: identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus.1999In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 18, p. 342-354Article in journal (Refereed)
  • 37. Gessner, Bradford D
    et al.
    Wilder-Smith, Annelies
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Institute of Public Health, University of Heidelberg, Germany.
    Estimating the public health importance of the CYD-tetravalent dengue vaccine: vaccine preventable disease incidence and numbers needed to vaccinate2016In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 34, no 20, p. 2397-2401Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To evaluate the potential public health impact of the live attenuated tetravalent Sanofi Pasteur dengue vaccine (CYD-TDV) we analyzed data from the reported clinical trials to calculate vaccine preventable disease incidence (VPDI) and number needed to vaccinate (NNV) based on the licensure indication for persons age 9 years and above.

    METHODS: VPDI is defined as incidence in an unvaccinated population X vaccine efficacy (VE), and thus incorporates both VE and the underlying burden of disease. NNV was calculated as 100,000 divided by VPDI divided by 2-year length of study. We compared these values to data for three newer vaccines that are currently integrated into some national immunization programs in Asia and Latin America, namely pneumococcal conjugate, Haemophilus influenzae type b, and rotavirus vaccines.

    RESULTS: In the Asian-Pacific trial, in the first 25 months after the first dose of the dengue vaccine, CYD-TDV prevented annually 2639 cases of virologically confirmed dengue for every 100,000 persons vaccinated, for an NNV of 18. In the Latin American trial, given the overall lower annual dengue incidence compared to Asia, VPDI was 1707, and NNV 28. For the Asian-Pacific and Latin American studies, the VPDIs for hospitalized virologically confirmed disease at the trials' end were 638 and 239 per 100,000 population per year, respectively, with NNVs of 75 and 201. VPDI for confirmed dengue hospitalization was higher than that for Hib vaccine against Hib meningitis or all cause severe pneumonia while lower than that for rotavirus vaccine against severe rotavirus gastroenteritis.

    CONCLUSIONS: Our analysis found that the CYD-TDV dengue vaccine had favorable VPDI and NNV, also when compared to existing vaccines used in Latin America and Asia. VPDI and NNV varied by serotype distribution, extent of prior dengue exposure (baseline seroprevalence) and country. These findings will help policy-makers decide where and how to introduce this vaccine post-licensure.

  • 38. Giha, Hayder A
    et al.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Balogun, Halima A
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Arnot, David
    Theander, Thor G
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Elghazali, Gehad
    Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 7, p. 1732-1739Article in journal (Refereed)
    Abstract [en]

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years. After an initial analysis, the immune response to Pf332-C231 antigen was the only one found associated with protection, thus taken for further analysis. The number of previous clinical malaria episodes experienced by the donors was used as an index for relative protection. The number of these episodes was found to be negatively correlated with the levels of pre-existing total IgG, IgG2 and IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195, p=0.023 and CC - 0.211, p=0.014, respectively), and also with age (CC - 0.311, p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by both patent and sub-patent infections regardless of the number of previous malaria episodes (1-7). Combining the correlation analysis with a multi-linear regression, three variable markers for protection were emerged, two age-dependent, the antibody response to Pf332-C231 and an unidentified marker (likely immune response to other antigens), and the third was an age-independent unidentified marker (possibly gene polymorphisms). In conclusion, this report suggests a protective effect for IgG subclasses to Pf332-C231 antigen against malaria.

  • 39. Goetsch, L.
    et al.
    Plotnicky-Gilquin, H.
    Champion, T.
    Beck, A.
    Corvaia, N.
    Ståhl, Stefan
    KTH, Superseded Departments, Biotechnology.
    Bonnefoy, J. Y.
    Nguyen, T. N.
    Power, U. F.
    Influence of administration dose and route on the immunogenicity and protective efficacy of BBG2Na, a recombinant respiratory syncytial virus subunit vaccine candidate2000In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 18, no 24, p. 2735-2742Article in journal (Refereed)
    Abstract [en]

    The immunogenicity and protective efficacy of BBG2Na, a novel recombinant respiratory syncytial virus subunit vaccine candidate, was assessed in BALB/c mice under various conditions of dose, administration route and number of immunisations. A single intra-peritoneal (i.p.) dose of 2 mu g, or two doses of 0.2 mu g, were sufficient to induce elevated RSV-A serum antibodies and sterilising lung protective immunity. Serum antibody titres were significantly boosted following second immunisations, but not a third. Of three routes of immunisation, i.p. induced the highest RSV-A antibody titres, followed in efficacy by the intramuscular (i.m.) and subcutaneous (s.c.) routes. Nonetheless, all three routes induced comparable and sterilising lung protection. In contrast, upper respiratory tract protection was observed only after i.p. vaccination, although significant viral titre reductions were evident following i.m. or s.c. immunisations. Interestingly, Pepscan analyses indicated that antibody epitope usage was highest in i.p. and lowest in i.m. immunised mice, respectively. Nonetheless, all routes resulted in antibody responses to known lung protective epitopes (protectopes). Thus, the prevention of serious lower respiratory tract disease, the principle goal of a RSV vaccine, but not URT infection, is dose dependent but unlikely to be influenced by the route of BBG2Na administration.

  • 40.
    Gottvall, Maria
    et al.
    Uppsala universitet, Vårdvetenskap.
    Tydén, Tanja
    Uppsala universitet, Vårdvetenskap.
    Larsson, Margareta
    Uppsala universitet, Institutionen för kvinnors och barns hälsa.
    Stenhammar, Christina
    Uppsala universitet, Institutionen för kvinnors och barns hälsa.
    Höglund, Anna T
    Uppsala universitet, Centrum för forsknings- och bioetik.
    Challenges and opportunities of a new HPV immunization program: Perceptions among swedish school nurses2011In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 29, p. 4576-4583Article in journal (Refereed)
    Abstract [en]

    Aim To investigate school nurses’ perceptions of HPV immunization, and their task of administering the vaccine in a planned school-based program in Sweden. Method: Data were collected through five focus group interviews with school nurses (n = 30). The interviews were recorded, transcribed verbatim and analyzed using content analysis.

    Findings The theme Positive attitude to HPV immunization despite many identified problems and challenges summarizes the results. The school nurses saw the program as a benefit in that the free school-based HPV immunization program could balance out social inequalities. However, they questioned whether this new immunization program should be given priority given their already tight schedule. Some also expressed doubts regarding the effect of the vaccine. It was seen as challenging to obtain informed consent as well as to provide information regarding the vaccine. The nurses were unsure of whether boys and their parents should also be informed about the immunization.

    Conclusion Although some positive aspects of the new HPV immunization program were mentioned, the school nurses primarily identified problems and challenges; e.g. regarding priority setting, informed consent, culture and gender. In order to achieve a good work environment for the school nurses, and obtain a high coverage rate for the HPV immunization, these issues need to be taken seriously, be discussed and acted upon.

  • 41.
    Gottvall, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stenhammar, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Höglund, Anna T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Challenges and opportunities of a new HPV immunization program: Perceptions among swedish school nurses2011In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 29, p. 4576-4583Article in journal (Refereed)
    Abstract [en]

    Aim To investigate school nurses’ perceptions of HPV immunization, and their task of administering the vaccine in a planned school-based program in Sweden. Method: Data were collected through five focus group interviews with school nurses (n = 30). The interviews were recorded, transcribed verbatim and analyzed using content analysis.

    Findings The theme Positive attitude to HPV immunization despite many identified problems and challenges summarizes the results. The school nurses saw the program as a benefit in that the free school-based HPV immunization program could balance out social inequalities. However, they questioned whether this new immunization program should be given priority given their already tight schedule. Some also expressed doubts regarding the effect of the vaccine. It was seen as challenging to obtain informed consent as well as to provide information regarding the vaccine. The nurses were unsure of whether boys and their parents should also be informed about the immunization.

    Conclusion Although some positive aspects of the new HPV immunization program were mentioned, the school nurses primarily identified problems and challenges; e.g. regarding priority setting, informed consent, culture and gender. In order to achieve a good work environment for the school nurses, and obtain a high coverage rate for the HPV immunization, these issues need to be taken seriously, be discussed and acted upon.

  • 42.
    Griffin, Paul
    et al.
    QIMR Berghofer Medical Research Institute, Australia; Q Pharm Pty Ltd, Australia; Mater Hospital and Mater Research, Australia; University of Queensland, Australia.
    Elliott, Suzanne
    Q Pharm Pty Ltd, Australia.
    Krauer, Kenia
    Q Pharm Pty Ltd, Australia.
    Davies, Cristyn
    University of Sydney, Australia; Childrens Hospital Westmead, Australia.
    Rachel Skinner, S.
    University of Sydney, Australia; Childrens Hospital Westmead, Australia.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Forster, Angus
    Vaxxas Pty Ltd, Australia.
    Safety, acceptability and tolerability of uncoated and excipient-coated high density silicon micro-projection array patches in human subjects2017In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, no 48, p. 6676-6684Article in journal (Refereed)
    Abstract [en]

    Most vaccinations are performed by intramuscular injection with a needle and syringe. However, this method is not ideal due to limitations, such as the risk of needle-stick injury, the requirement for trained personnel to give injections and the need to reconstitute lyophilized vaccines. Therefore, we tested an alternative delivery technology that overcomes the problems with needle and syringe. The Nanopatch (TM) is an array of 10,000 silicon micro-projections per cm(2) that can be dry-coated with vaccine for skin delivery. The high number and density of micro-projections means that high velocity application is required to achieve consistent skin penetration. Before clinically testing a vaccine Nanopatch, this study tests the safety, tolerability and acceptability/utility of uncoated and excipient-coated Nanopatches in healthy adults. Nanopatches were applied to skin of the upper arm and volar forearm and left in contact with the skin for two minutes before removal. The application sites were assessed for local skin response over 28 days. Acceptability interviews were also performed. No unexpected adverse events directly related to the Nanopatch application were reported, All applications of the Nanopatch resulted in an expected erythema response which faded between days 3 and 7. In some subjects, some skin discolouration was visible for several days or up to 3 weeks after application. The majority (83%) of subjects reported a preference for the Nanopatch compared to the needle and syringe and found the application process to be simple and acceptable. On a pain scale from 0 to 10, 78% of applications were scored "0" (no pain) with the average scores for less than 1. The results from this study demonstrate the feasibility of the Nanopatch to improve vaccination by showing that application of the product without vaccine to human skin is safe, tolerable and preferred to needle and syringe administration. (C) 2017 The Authors. Published by Elsevier Ltd.

  • 43. Harrison, Lee H
    et al.
    Pelton, Stephen I
    Wilder-Smith, Annelies
    Institute of Public Health, University of Heidelberg, Germany.
    Holst, Johan
    Safadi, Marco A P
    Vazquez, Julio A
    Taha, Muhamed-Kheir
    LaForce, F Marc
    von Gottberg, Anne
    Borrow, Ray
    Plotkin, Stanley A
    The global Meningococcal initiative: recommendations for reducing the global burden of meningococcal disease2011In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 29, no 18, p. 3363-3371Article in journal (Refereed)
    Abstract [en]

    The Global Meningococcal Initiative (GMI) is composed of an international group of scientists, clinicians and public health officials with expertise in meningococcal immunology, epidemiology and prevention. The primary goal of the GMI is the promotion of the global prevention of invasive meningococcal disease through education and research. The GMI members reviewed global meningococcal disease epidemiology, immunization strategies, and research needs. Over the past decade, substantial advances in meningococcal vaccine development have occurred and much has been learned about prevention from countries that have incorporated meningococcal vaccines into their immunization programs. The burden of meningococcal disease is unknown for many parts of the world because of inadequate surveillance, which severely hampers evidence-based immunization policy. As the field of meningococcal vaccine development advances, global surveillance for meningococcal disease needs to be strengthened in many regions of the world. For countries with meningococcal vaccination policies, research on vaccine effectiveness and impact, including indirect effects, is crucial for informing policy decisions. Each country needs to tailor meningococcal vaccination policy according to individual country needs and knowledge of disease burden. Innovative approaches are needed to introduce and sustain meningococcal vaccination programs in resource-poor settings with a high incidence of meningococcal disease.

  • 44. Hertzell, Katarina Brodin
    et al.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Vene, Sirkka
    Askling, Helena H
    Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumatoid arthritis: A prospective, open-label, multi-centre study2016In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 34, no 5, p. 650-655Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX).

    METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test.

    RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05).

    CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.

  • 45.
    Hinkula, Jorma
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Hagbom, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Wahren, Britta
    Swedish Institute for Infectious Disease Control Microbiology and Tumorbiology Center Karolinska Institute, Solna.
    Schröder, Ulf
    Eurocine AB Karolinska Science Park, Stockholm.
    Safety and immunogenicity, after nasal application of HIV-1 DNA gagp37 plasmid vaccine in young mice2008In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 40, p. 5101-5106Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for safe and potent adjuvants capable of delivering vaccine candidates over the mucosal barrier, with good capacity to stimulate both mucosal and systemic cell-mediated and humoral immunity. An adjuvant aimed for intranasal delivery should preferably deliver the antigen and minimize the transfer into the close proximity of the central nervous system, thus avoiding damage on the olfactory tissues. Advantages with a mucosal delivery route would be to provide mucosal and systemic immunity, requiring lower vaccine doses then when given parentally. The aim of this study was to study if the N3 adjuvant intranasally administered with HIV DNA plasmids would be transferred into the olfactory tissues and cause local inflammation and tissue damage. Results: The N3 adjuvant alone and when combined with HIV-1 DNA gag plasmid and delivered intranasally did not cause detectable damage to the nasal epithelium or the olfactory epithelium or bulb over a period of 3 days after delivery. The intranasal administration of HIV-1 gagp37 DNA induced both a humoral and a cell-mediated immunity against the gag antigen. Significantly higher HIV-1-specific humoral, but not cell-mediated immune responses were seen in DNA/N3-immunized mice in comparison with HIV-1 DNA/saline-immunized animals. Conclusions: A safe and convenient intranasal mode of HIV-1 DNA plasmid and adjuvant delivery was shown not to interfere with the tissues in close proximity to the central nervous system. The N3 adjuvant combined with HIV-1 plasmids enhances the HIV-1-specific immunogenicity and merits to be clinically tested. © 2008 Elsevier Ltd. All rights reserved.

  • 46.
    Huijbers, Elisabeth J M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Femel, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Björkelund, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The non-toxic and biodegradable adjuvant Montanide ISA 720/CpG can replace Freund's in a cancer vaccine targeting ED-B-a prerequisite for clinical development2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 2, p. 225-230Article in journal (Refereed)
    Abstract [en]

    We have recently shown that immunization against the extra domain-B (ED-B) of fibronectin, using Freund's adjuvant, reduces tumor growth in mice by 70%. In the present study we compare the immune response generated against ED-B using the non-toxic and biodegradable adjuvant Montanide ISA 720/CpG with the response elicited by Freund's adjuvant. Montanide ISA 720/CpG induced anti-ED-B antibodies with higher avidity and less variable levels between individuals than Freund's. Moreover, the duration of the immune response was longer and the generation of anti-ED-B antibodies in naïve mice was faster, when Montanide ISA 720/CpG was used. We conclude that it is possible to replace the mineral oil based adjuvant Freund's with an adjuvant acceptable for human use, which is a prerequisite for transfer of the ED-B vaccine to the clinic.

  • 47.
    Iriemenam, Nnaemeka C.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Khirelsied, Atif H.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    ElGhazali, Gehad
    Giha, Haider A.
    Elhassan A-Elgadir, Thoraya
    Agab-Aldour, Ahmed A.
    Montgomery, Scott M.
    Anders, Robin F.
    Theisen, Michael
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Elbashir, Mustafa I.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 1, p. 62-71Article in journal (Refereed)
    Abstract [en]

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

  • 48. Iriemenam, Nnaemeka C.
    et al.
    Khirelsied, Atif H.
    Nasr, Amre
    ElGhazali, Gehad
    Giha, Haider A.
    Elhassan A-Elgadir, Thoraya M.
    Agab-Aldour, Ahmed A.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Anders, Robin F.
    Theisen, Michael
    Troye-Blomberg, Marita
    Elbashir, Mustafa I.
    Berzins, Klavs
    Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 1, p. 62-71Article in journal (Refereed)
    Abstract [en]

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

  • 49.
    Istrate, Claudia
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Hinkula, Jorma
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Charpilienne, Annie
    Poncet, Didier
    Cohen, Jean
    Svensson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology .
    Johansen, Kari
    Parenteral administration of RF 8-2/6/7 rotavirus-like particles in a one-dose regimen induce protective immunity in mice2008In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 35, p. 4594-4601Article in journal (Refereed)
    Abstract [en]

    Rotavirus virus-like particles (RV-VLPs) represent a novel strategy for development of a rotavirus subunit vaccine. In this study, RF 8-2/6/7-VLPs with rotavirus VP8 protein (amino acid 1-241 of VP4) fused to the amino terminal end of a truncated VP2, were evaluated for their immunogenic and protective properties. A single intramuscular dose of, either 2 or 20 μg, RF 8-2/6/7-VLPs alone or combined with a potent adjuvant poly[di(carboxylatophenoxy)]phosphazene] (PCPP) induced rotavirus-specific serum IgG and IgA, fecal IgG titers that were enhanced 5-90-fold by adjuvant. Passive protective immunity was achieved in offspring to dams vaccinated with 2 and 20 μg RV-VLPs in presence of adjuvant and 20 μg RV-VLP without adjuvant. © 2008 Elsevier Ltd. All rights reserved.

  • 50. Jackson, Lisa A.
    et al.
    Gurtman, Alejandra
    Rice, Kathryn
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Greenberg, Richard N.
    Jones, Thomas R.
    Scott, Daniel A.
    Emini, Emilio A.
    Gruber, William C.
    Schmoele-Thoma, Beate
    Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, no 35, p. 3585-3593Article in journal (Refereed)
    Abstract [en]

    Background: The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13). Methods: We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination. Results: Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment. Conclusion: In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13. 

123 1 - 50 of 119
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf