Methods: We immunized 22 control and 19 newly-diagnosed HIV-1-infected adults (median 610 CD4+ T cells/µL (range: 139-1408) and 69,316 plasma HIV RNA (range 232-806,936) on ART for 1-4 months with PCV13. We measured 1) PPS-specific antibody-secreting cells (ASC) by ELISPOT at weeks 0 and 1, 2) serum IgG to 11 PPS serotypes (ST) by multiplex ELISA and 3) titers of opsonophagocytosis (OP) for 4 ST at wks 0 and 8, and 4) 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: Numbers 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 0-8 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 4 ST in both groups from weeks 0-8. In contrast, although DT-specific IgG ASC increased from weeks 0-1 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.
L. K. Nicholson,
E. M. Gardner, None
J. Rahkola, None
R. L. Burton, None
M. H. Nahm, None
E. N. Janoff, None