Experimental pneumococcal carriage reveals humoral correlates of susceptibility in virally suppressed adults with HIV

Abstract

Background People with HIV (PWH) in sub-Saharan Africa remain at high risk of pneumococcal carriage and disease, despite effective antiretroviral therapy. Understanding the immune factors driving this is key to addressing the issue. Methods Virally suppressed, clinically stable PWH (n = 60) and HIV-uninfected adults (n = 60) underwent intranasal challenge with live pneumococcus serotype 6B. Experimental carriage was determined by culture and serotyping of nasal wash samples. Pneumococcal capsular and whole-cell IgG in nasal wash and serum samples were measured by ELISA. Antibody binding was measured using a flow cytometry assay. Results Baseline pneumococcal capsular IgG, whole-cell IgG, and antibody binding were similar between PWH and HIV-uninfected participants. Challenge did not increase IgG concentration in either group. Carriage susceptibility among PWH was associated with lower baseline serum capsular 6B IgG (0.84 vs 2.33 µg/mL, p < 0.01), lower nasal capsular 6B IgG (328 vs 761 pg/mL, p = 0.07), and lower nasal whole-cell IgG (92.2 vs 205 AU/mL, p = 0.02). These associations were not observed in HIV-uninfected participants. Carriage in HIV-uninfected participants was associated with an increase in IgG binding from baseline to day 21 (120 vs 209 AU, Friedman χ2 = 11.1, p = 0.004), which was not detected in PWH (79.2 vs 72.3 AU, χ2 = 0.67, p = 0.72)). Conclusion Baseline pneumococcal IgG levels and function were similar in PWH and HIV-uninfected participants. However, experimental challenge revealed specific differences in humoral correlates of pneumococcal carriage between PWH and HIV-uninfected adults. These findings support evaluation of vaccination strategies to enhance pneumococcal antibody concentration and function in PWH in sub-Saharan Africa.