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Impact of the inflammatory response on specific immunity in neurosurgical patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Vaccination with a T-cell-dependent pneumococcal conjugate vaccine (PCV) followed by a T-cell-independent pneumococcal polysaccharide vaccine (PPSV) is recommended after basilar skull fracture to reduce the risk of meningitis. The optimal time frame for vaccination has not yet been established and varies widely in practice. Because the risk of meningitis is at its peak shortly after the trauma incident, early vaccination might be more desirable. After trauma and central nervous system (CNS) injury, T-cell defects leading to trauma and CNS injury-induced immune deficiency syndromes may affect the vaccine response. In light of the above information, the overall aim of this thesis was to investigate the impact of neurotrauma and neurosurgery on the response to T-cell-dependent and T-cell-independent vaccines.

In Paper I, we compared the antibody response to a T-cell-dependent conjugate vaccine in patients vaccinated within 10 days after neurotrauma or neurosurgery with those vaccinated after >3 weeks. To avoid interference with pneumococcal vaccination, a conjugate vaccine against Haemophilus influenzae type b (Hib) was chosen for the study. The majority of the patients responded to the vaccination, although the number of responders was significantly lower in patients vaccinated early.

In Paper II, we investigated the antibody response to the T-cell-independent vaccine PPSV in patients vaccinated within 10 days after neurotrauma or neurosurgery and in patients vaccinated after >3 weeks. Patients vaccinated early responded similarly to those vaccinated after the acute period, indicating that PPSV can be administered early after neurotrauma or neurosurgery.

In Paper III, we compared the response to Hib vaccine with the response to PPSV. We also examined whether individual clinical or immunological parameters might predict the response to T-cell-dependent vaccine and thereby help identify non-responders before vaccination. No correlation between Hib vaccine and PPSV responses was found, indicating that B-cell function is not similarly depressed as T-cell function. It was not possible to predict the T-cell-dependent vaccine response by standardized grading of the trauma or by parameters reflecting the innate immune response.

In Paper IV, we found a significant reduction in the ex vivo CD4+ T-lymphocyte response to PCV in patients after neurotrauma or neurosurgery as compared with healthy controls.

Our results suggest that PPSV might be a viable alternative to T-cell-dependent PCV in early vaccination after neurotrauma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 79
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1563
Keywords [en]
T-cell-dependent vaccine, T-cell-independent vaccine, CNS injury-induced immune deficiency syndrome, pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, posttraumatic meningitis.
National Category
Infectious Medicine
Research subject
Medical Science; Infectious Diseases
Identifiers
URN: urn:nbn:se:uu:diva-378929ISBN: 978-91-513-0626-1 (print)OAI: oai:DiVA.org:uu-378929DiVA, id: diva2:1300885
Public defence
2019-05-27, Sal IX, Universitetshuset, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-05-06 Created: 2019-03-30 Last updated: 2019-06-18
List of papers
1. Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults
Open this publication in new window or tab >>Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults
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2015 (English)In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 70, no 6, p. 577-584Article in journal (Refereed) Published
Abstract [en]

Background: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. Methods: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. Results: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log(10) anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 +/- 0.15, 1.38 +/- 0.15 and 1.81 +/- 0.12 mu g/ml, respectively. Conclusions: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Keywords
Neurotrauma, Meningitis, Conjugate vaccine
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-304603 (URN)10.1016/j.jinf.2014.12.014 (DOI)000354115600004 ()25562448 (PubMedID)
Available from: 2016-10-06 Created: 2016-10-06 Last updated: 2019-03-30Bibliographically approved
2. Pneumococcal polysaccharide vaccination administered early after neurotrauma or neurosurgery
Open this publication in new window or tab >>Pneumococcal polysaccharide vaccination administered early after neurotrauma or neurosurgery
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2017 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, no 6, p. 909-915Article in journal (Refereed) Published
Abstract [en]

Objectives: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). Methods: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10 days after neurotrauma or neurosurgery. Twenty-nine neurosurgical patients vaccinated >= 3 weeks after neurotrauma or neurosurgery served as controls. Serotype-specific anti-polysaccharide binding IgG antibody levels to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme immunoassay. Results: The vaccination was safe and a highly significant antibody response was found against all serotypes in all groups (p < 0.001 for each of the serotypes). There were no differences between groups or in the group by time interaction in any of the serotypes. After early and late vaccination, protective levels were found in >80% for serotypes 9V, 14, 18C, 19F and 23F and in 70% and 50% for serotypes 6B and 4, respectively. Conclusion: Patients vaccinated with PPSV within 10 days after neurotrauma or neurosurgery respond similarly to those vaccinated after >= 3 weeks, indicating that PPSV can be administered early after neurotrauma or neurosurgery.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2017
Keywords
Pneumococcal polysaccharide vaccine, Neurotrauma, Neurosurgery
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-319568 (URN)10.1016/j.vaccine.2016.12.065 (DOI)000394196000010 ()28069358 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2019-03-30Bibliographically approved
3. Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma; Can the response be predicted?
Open this publication in new window or tab >>Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma; Can the response be predicted?
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(English)Manuscript (preprint) (Other academic)
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-380638 (URN)
Available from: 2019-03-30 Created: 2019-03-30 Last updated: 2019-03-30
4. Decreased T-lymphocyte response to T-cell-dependent vaccines after neurotrauma or neurosurgery
Open this publication in new window or tab >>Decreased T-lymphocyte response to T-cell-dependent vaccines after neurotrauma or neurosurgery
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(English)Manuscript (preprint) (Other academic)
National Category
Infectious Medicine
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:uu:diva-380640 (URN)
Available from: 2019-03-30 Created: 2019-03-30 Last updated: 2019-03-30

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