642. B and T cell Responses to Pneumococcal Polysaccharide and Protein Vaccine Antigens in Recently-Diagnosed HIV-1-Infected Patients
Session: Poster Abstract Session: Pathogenesis and Immune Response
Thursday, October 4, 2018
Room: S Poster Hall
Background: 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: 139-1408) 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.

Lindsay K. Nicholson, MD1, Vibha Jha, PhD2, Edward M. Gardner, MD3, Jeremy Rahkola, BS2, Robert L. Burton, BS4, Moon H. Nahm, MD5 and Edward N. Janoff, MD, FIDSA6, (1)Infectious Diseases, University of Colorado Denver, Aurora, CO, (2)Infectious Diseases, University of Colorado – Denver, Aurora, CO, (3)Denver Public Health, Denver, CO, (4)University of Alabama at Birmingham, Birmingham, AL, (5)Department of Med., Univ. of Alabama at Birmingham, Birmingham, AL, (6)University of Colorado Denver, Aurora, CO

Disclosures:

L. K. Nicholson, None

V. Jha, None

E. M. Gardner, None

J. Rahkola, None

R. L. Burton, None

M. H. Nahm, None

E. N. Janoff, None

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