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JOhtola Dissertation.pdf (1.84 MB)
ETD Abstract Container
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Pneumococcal Vaccination in Aging HIV-Infected Individuals
Author Info
Ohtola, Jennifer A
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=mco1435076215
Abstract Details
Year and Degree
2015, Doctor of Philosophy (PhD), University of Toledo, Biomedical Sciences (Infection, Immunity, and Transplantation).
Abstract
Advanced age and human immunodeficiency virus (HIV) infection are both risk factors for
Streptococcus pneumoniae
infections due to immunological dysfunction. The aging HIV-infected (HIV+) population may be at higher risk for pneumococcal disease due to the combination of these factors on humoral immunity. Current recommendations for pneumococcal vaccination in HIV+ adults include a priming dose of the 13-valent pneumococcal conjugate vaccine followed by one dose of the 23-valent pneumococcal polysaccharide vaccine 8 weeks later (PCV/PPV). We compared quantitative and qualitative antibody responses to PCV/PPV versus a single dose of PPV in HIV+ adults aged 50-65 years with CD4+ T cells/µl (CD4) >200 on antiretroviral therapy ≥1 year. We found that PCV/PPV did not demonstrate a clear immunological advantage to PPV alone, as serotype-specific IgG levels and functional titers postvaccination were similar between groups. In addition, these antibody responses were significantly reduced in HIV+ subjects vaccinated with PCV/PPV compared to age-matched, uninfected (HIV–) controls who received PCV/PPV. We also characterized the phenotype and surface expression of several receptors on serotype-specific B cells that may influence vaccine responses. HIV+ subjects vaccinated with PCV/PPV generated significantly reduced frequencies of circulating serotype-specific B cells postvaccination compared to those who received PPV only. However, phenotypic distributions of serotype-specific memory B cell subsets were similar between groups. Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI)+ serotype-specific B cell percentages were significantly decreased in HIV+ PCV/PPV compared to PPV groups, indicating that prior PCV altered TACI expression. It remains unclear if this impact provides any benefit to vaccine responses. CD21+ serotype-specific B cells were also significantly reduced in HIV+ compared to HIV– PCV/PPV groups which may contribute to diminished antibody responses. Collectively, our findings suggest that continued efforts aimed at developing more effective vaccination strategies in susceptible adult populations are warranted, and further investigation into the immunological mechanisms that increase the risk of pneumococcal disease and induce potent vaccine responses are necessary.
Committee
M. A. Julie Westerink, MD (Advisor)
Deepak Malhotra, MD, PhD (Committee Member)
Z. Kevin Pan, MD, PhD (Committee Member)
Stanislaw Stepkowski, DVM, PhD, DSc (Committee Member)
R. Mark Wooten, PhD (Committee Member)
Pages
124 p.
Subject Headings
Immunology
;
Microbiology
Keywords
Streptococcus pneumoniae
;
pneumococcal conjugate vaccine
;
pneumococcal polysaccharide vaccine
;
HIV infection
;
aging
;
B cells
;
antibody
Recommended Citations
Refworks
EndNote
RIS
Mendeley
Citations
Ohtola, J. A. (2015).
Pneumococcal Vaccination in Aging HIV-Infected Individuals
[Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1435076215
APA Style (7th edition)
Ohtola, Jennifer.
Pneumococcal Vaccination in Aging HIV-Infected Individuals.
2015. University of Toledo, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=mco1435076215.
MLA Style (8th edition)
Ohtola, Jennifer. "Pneumococcal Vaccination in Aging HIV-Infected Individuals." Doctoral dissertation, University of Toledo, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1435076215
Chicago Manual of Style (17th edition)
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Document number:
mco1435076215
Download Count:
450
Copyright Info
© 2015, some rights reserved.
Pneumococcal Vaccination in Aging HIV-Infected Individuals by Jennifer A Ohtola is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.