Race-related differences in functional antibody response to pneumococcal vaccination in HIV-infected individuals

Abstract

Background: Both HIV positivity and African American (AA) ethnicity are associated with increased incidence of invasive pneumococcal disease (IPD). Poor immune response to pneumococcal polysaccharide-based vaccines may contribute to the race related increased frequency of IPD in African American HIV positive individuals.

Methods: Caucasian and AA HIV-infected (HIV+) individuals 40-65 years old with CD4+ T cells/µl (CD4) >200 on antiretroviral therapy (ART) received either the 13-valent pneumococcal conjugate vaccine (PCV) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV) or PPV only. Serum IgG, IgM and opsonophagocytic antibody responses to serotypes 14 and 23F as well as serum IgG and opsonophagocytic antibody responses to serotype 19A were measured pre- and post-vaccination. We measured serum markers of inflammation in all participants and performed single cell gene expression profiling at the baseline by HD Biomark in Caucasians and African Americans.

Results: There were no significant differences in pre-immunization inflammatory markers or post-vaccination IgG and IgM concentrations between Caucasian and African American participants. However, we found significantly lower opsonophagocytic activity in response to serotypes 14 and 19A in the AA group compared to the Caucasian group. There was no association between inflammatory markers and immune response to vaccination, however we found extensive biomodal variation in gene expression levels in single IgM+ memory B cells. Differentially expressed genes may be related to differences in the immune response between ethnic groups.

Conclusions: Distinct racial differences were found in the functional immune response following either PPV and/or PCV/PPV immunization in HIV-positive adults, although these differences were serotype dependent. Decreased ability to respond to vaccination may in part explain racial disparities in pneumococcal disease epidemiology. ClinicalTrials.gov ID: NCT03039491.

Keywords: B cells; HIV infection; Pneumococcal conjugate vaccine; Pneumococcal polysaccharide vaccine; Racial disparities; Streptococcus pneumoniae.

Conflict of interest statement

Conflict of Interest: All authors have no potential conflicts of interest.

Declaration of interests

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Table: see text]

Published by Elsevier Ltd.

Figures

Figure 1.. Polysaccharide-specific serum antibody levels to serotypes 14, 23F and 19A.

Serum IgG and IgM antibody responses tested for PPS14, PPS23F, and 19A in Caucasian and African American HIV-positive individuals pre- and post-immunization with Pneumovax-23 (PPV) or Prevnar-13/Pneumovax-23 (PCV/PPV). Changes in serum antibody levels in a single group were compared using paired t-test and changes between the groups were compared using Wilcoxon sign rank t-test.

Figure 2.. Serum OPA titers to serotypes 14, 23F, and 19A.

Serotype-specific serum OPA titers were determined in HIV-positive Caucasian and African-American individuals pre-and post-vaccination with either A-Pneumovax-23 (PPV) or B-Prevnar-13 (PCV)/Pneumovax-23 (PCV/PPV). All Caucasian versus African American participants in groups A and B together depicted in C. Changes in OPA titers in a single group were compared using paired t-test and changes between the groups were compared using Wilcoxon sign rank t-test.

Figure 3.

Correlation between post-vaccination IgG antibody levels and OPA titers in all HIV-positive African-American and Caucasian individuals regardless of vaccination protocol. Correlations were determined by Pearson’s correlation coefficient.

Figure 4.. Serum cytokine and chemokine levels.

Serum inflammatory markers were measured using Luminex assay in HIV-positive African-American and Caucasian individuals prior to immunization. Difference between the groups were compared using Wilcoxon sign rank test; no significant differences were found.

Figure 5.. Multimodal variation in gene expression levels.

Violin plots of differentially expressed genes that are ranked by p-values. 64 genes were examined in pre-immunization IgM memory single B cells isolated from HIV-positive African-American and Caucasian individuals.