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

Abstract

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.

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

Figure 1. Total and pneumococcal polysaccharide-specific memory CD19⁺ B cell subset percentages to the indicated serotypes in HIV-infected and HIV-uninfected subjects

Percentages of total and serotype-specific IgM memory (CD19⁺CD27⁺IgM⁺, upper panels) and switched memory (CD19⁺CD27⁺IgM⁻, lower panels) B cell subsets were measured by flow cytometry in HIV-infected PPV (PPS14, n=17; PPS23F, n=19), HIV-infected PCV/PPV (PPS14 and PPS23F, n=15), and HIV-uninfected PCV/PPV (PPS14, n=13; PPS23F, n=14) groups. PCV/PPV groups received PCV followed by PPV 8 weeks later. Graphs represent total B cell percentages at baseline and serotype-specific B cell percentages 1 week after vaccination with PPV (post-PPV). Left panels represent PPS14-specific B cell percentages and right panels represent PPS23F-specific B cell percentages. Scatter dot plots include median (horizontal black line) with interquartile range. Abbreviations: PPS, pneumococcal polysaccharide; HIV, human immunodeficiency virus; PPV, 23-valent pneumococcal polysaccharide vaccine; PCV, 13-valent pneumococcal conjugate vaccine. *P<0.05, **P<0.01, ***P<0.001.

Figure 2. Surface expression of B cell receptors on total and pneumococcal polysaccharide-specific CD19⁺ B cells in HIV-infected and HIV-uninfected subjects

Percentages of BAFF-R, TACI, CD21, and CD40 positive total and PPS23F-specific CD19⁺ B cells were determined by flow cytometry in HIV+ PPV (n=11), HIV+ PCV/PPV (n=15), and HIV− PCV/PPV (n=16) subjects. PCV/PPV groups received PCV followed by PPV 8 weeks later. Graphs represent total B cell percentages at baseline and serotype-specific B cell percentages 1 week after vaccination with PPV (post-PPV). Scatter dot plots include median (horizontal black line) with interquartile range. Abbreviations: PPS, pneumococcal polysaccharide; HIV, human immunodeficiency virus; PPV, 23-valent pneumococcal polysaccharide vaccine; PCV, 13-valent pneumococcal conjugate vaccine. *P<0.05, **P<0.01, ***P<0.001.