642. B- and T-Cell Responses to Pneumococcal Polysaccharide and Protein Vaccine Antigens in Recently Diagnosed HIV-1-Infected Patients

BACKGROUNDS: Prevention of serious HIV-1-associated pneumococcal infections may be compromised by the limited magnitude and function of vaccine-induced antibodies. Responses to the T-independent pneumococcal capsular polysaccharide (PPS) + T-dependent diphtheria toxoid (DT) protein conjugate vaccine (PCV-13) may be influenced by CD4+ T follicular helper (TFH) cells which provide specific help for B-cell differentiation. METHODS: We immunized 22 control and 19 newly diagnosed HIV-1-infected adults (median 610 CD4+ T cells/µL (range: 139–1,408) and 69,316 plasma HIV RNA (range 232-806,936) on ART for 1–4 months with PCV13. We measured (i) PPS-specific antibody-secreting cells (ASC) by ELISPOT at Weeks 0 and 1, (ii) serum IgG to 11 PPS serotypes (ST) by multiplex ELISA and (iii) titers of opsonophagocytosis (OP) for four STs at Weeks 0 and 8, and (iv) numbers and activation (ICOS expression) of circulating TFH cells by flow cytometry at Weeks 0 and 1. Values were compared by ANOVA, paired and unpaired t and Mann–Whitney tests. RESULTS: The number of PPS-specific IgG, IgM and IgA ASC increased significantly from Weeks 0 to 1 post-PCV13 and to similar magnitude in both Controls and HIV+ subjects, returning to baseline by Week 8. Levels of serum PPS-specific IgG increased significantly from Weeks 0 to 8 for 10/11 vs. 7/11 ST in controls and HIV+ subjects, respectively (P = NS), and to comparable levels. Similarly, OP titers increased significantly and similarly to each of four STs in both groups from Weeks 0 to 8. In contrast, although DT-specific IgG ASC increased from Weeks 0 to 1 in HIV+ and controls, these values were lower among HIV-1+ adults (P = .001). Consistent with these limited responses, a key regulatory molecule on TFH cells, elicited largely by T-dependent antigens (DT), was upregulated on cells from Control but not HIV+ at Week 1. Moreover, levels of IL-12, which drives TFH differentiation, were also lower among HIV-1+ at Week 1. Conclusion. Humoral responses to PPS are largely intact (ASC, serum IgG and killing function) with recently diagnosed HIV-1 infection, highlighting the importance of early HIV-1 recognition. That responses to T-dependent DT and TFH activation are more limited, even with high CD4+ counts and ART, suggests a more rapid and perhaps more recalcitrant HIV-1-associated T-cell defect. DISCLOSURES: All authors: No reported disclosures.