Quantitative and Functional Antibody Responses to the 13-Valent Conjugate and/or 23-Valent Purified Polysaccharide Vaccine in Aging HIV-Infected Adults.

BACKGROUND: The number of aging human immunodeficiency virus-infected (HIV+) individuals living in the United States has substantially grown over the past two decades. Advanced age and HIV infection both increase susceptibility to Streptococcus pneumoniae infection due to B cell dysfunction. The combined impact of these factors on pneumococcal vaccine responses remains unknown. METHODS: We assessed serum immunoglobulin (Ig) G and IgM levels and opsonophagocytic killing assay (OPA) titers to pneumococcal serotypes 14 and 23F in HIV+ subjects and HIV-uninfected (HIV-) controls 50-65 years old. HIV+ individuals with CD4+ T cells/µl (CD4) >200 and ≥1 year of antiretroviral therapy (ART) received either a dose of the 13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine 8 weeks later (PCV/PPV) as currently recommended (n=15) or a single dose of PPV only (n=22). HIV- controls received PCV/PPV (n=14). RESULTS: HIV+ PCV/PPV and PPV groups exhibited similar increases in IgG levels and OPA titers for both serotypes after immunization. Postvaccination IgM levels for serotype 23F, but not 14, were significantly higher in HIV+ PCV/PPV compared to PPV groups. IgG and IgM levels for serotype 14 and OPA titers to serotype 23F were significantly reduced in HIV+ compared to HIV- PCV/PPV groups. Serotype-specific IgG levels correlated with OPA titers for all groups. CONCLUSIONS: Our data suggest that the recommended PCV/PPV regimen may not significantly improve quantitative or functional antibody responses compared to PPV only in aging HIV+ subjects. Continued efforts aimed at improving vaccine responses in this high risk population are warranted.

Inflammatory Markers and Immune Response to Pneumococcal Vaccination in HIV-Positive and -Negative Adults.

BACKGROUND: Members of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in the response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation in their expression is associated with an enhanced risk for pneumococcal disease in neonates but their expression in other high-risk populations including HIV-positive individuals remains to be elucidated. OBJECTIVE: To investigate signals that contribute towards PPS-response and identify potential anomalies that may account for diminished serological response in HIV-positive individuals post Pneumovax (PPV23) immunization. METHODS: Markers of inflammation, C-reactive protein (CRP), IL-6, sCD27 and sCD30, were assessed in HIV-positive and -negative individuals as potential predictors of PPV23 response. Serum levels of B cell activating factor (BAFF), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B cell maturation antigen (BCMA) and B cell expression of BAFF-R, TACI, BCMA, CD40 and CD21 were assessed in total (unselected) and PPS23F (antigen)-specific B cells of PPV23 immunized HIV-positive and -negative individuals. RESULTS: CRP, sCD27, sCD30 and BAFF were significantly elevated in the serum of HIV-positive individuals but did not adversely affect PPV23 response. Assessment of PPS-specific B cells revealed enhanced TACI and reduced BAFF-R expression compared to unselected B cells in HIV-positive and -negative individuals. Surface TACI was similar but soluble TACI was significantly lower in HIV-positive compared to HIV-negative individuals. CONCLUSION: Current studies highlight a potential role for TACI in PPV23 response based on its enhanced expression on PPS-specific B cells. Although surface levels of TACI were similar, diminished soluble TACI (sTACI) in HIV-positive compared to HIV-negative individuals could potentially decrease BAFF responsiveness and Ig response. A better understanding of the role of TNF receptors could contribute to the design of improved pneumococcal vaccines. TRIAL REGISTRATION: ClinicalTrials.gov NCT02515240.

Alterations in serotype-specific B cell responses to the 13-valent pneumococcal conjugate vaccine in aging HIV-infected adults.

BACKGROUND: Advanced age and human immunodeficiency virus (HIV) infection are associated with increased pneumococcal disease risk. The impact of these factors on cellular responses to vaccination is unknown. METHODS: HIV-infected (HIV+) individuals 50-65 years old with CD4(+) Tcells/µl (CD4) >200 on antiretroviral therapy (ART) ≥1 year received either the 13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine (PCV/PPV) or PPV only. HIV-uninfected (HIV-) controls received PCV/PPV. Phenotype distribution and surface expression of complement receptor CD21 and tumor necrosis factor superfamily receptors (TNFRs) were compared on serotype-specific B cells postvaccination. RESULTS: Postvaccination serotype-specific B cell percentages were significantly lower in HIV+ PCV/PPV compared to PPV groups, but similar between HIV+ or HIV- PCV/PPV 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. CD21(+) serotype-specific B cells were significantly higher in HIV- compared to HIV+ PCV/PPV groups. CONCLUSIONS: An initial dose of PCV reduced the frequency, but not phenotype distribution, of serotype-specific B cells and also lowered TACI expression in aging HIV+ subjects postvaccination with PPV. These findings suggest that PCV does not enhance cellular responses to revaccination with PPV.