Date of Award

2017

Document Type

Thesis

Department

Microbiology and Immunology

College

College of Graduate Studies

First Advisor

M. A. Julie Westerink

Second Advisor

Steven W. Kubalak

Third Advisor

Laura M. Kasman

Fourth Advisor

Wei Jiang

Abstract

Introduction: Streptococcus pneumoniae is a major cause of morbidity and mortality in HIV-positive individuals. Despite the widespread use of anti-retroviral medications, the incidence of pneumococcal disease is 20-40 fold higher in the HIV+ population compared to HIV- persons. Consequently, pneumococcal vaccination is recommended for all HIV+ individuals. In 2012 the FDA changed vaccine recommendation from a single vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) to a dual vaccination with 13-valent protein conjugate vaccine (PCV13) followed by PPV23. Studies demonstrating superiority of the PCV13/PPV23 regimen compared to PPV23 alone are limited and controversial. The goal of this study was to analyze and compare the immune response to PCV13/PPV23 versus PPV23 in HIV-positive individuals and age-matched HIV-negative persons. Methods: The participants for this study were recruited from the University of Toledo and MUSC. We focused on aging HIV+ persons and all participants were 50-64 years of age. Participants were randomized to either PCV13 followed by PPV23 group or PPV23 only. Blood samples were collected prior to vaccination and thirty days following the administration of PPV23 to analyze antibody responses and opsonophagocytic activity (OPA) to pneumococcal serotypes 3, 7 and 19A. Inflammatory markers were quantified by Luminex using serum samples on day 0. Results/Conclusions: OPA and pneumococcal-specific IgG antibody titers increased significantly from pre- to post-vaccination in all groups. In HIV+ subjects, there was no significant difference in antibody or OPA responses to serotypes 3, 7F or 19A comparing PCV/PPV to PPV alone In HIV-negative subjects, there was a significantly higher antibody response to serotype 19A only, but not to serotypes 3 and 7F in the group immunized with PCV13/PPV23. However, no significant differences were observed in OPA between groups (which groups?). Serum IP-10, TNF-alpha, IL-6, sCD40L, and APRIL were significantly higher in HIV+ compared to HIV-negative subjects. There were no correlations between any of the tested inflammatory markers and post-vaccination functional antibody response.

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