Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 3, Pages 994-1005Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500083
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Funding
- National Institutes of Health Grants [PO1 AI088575, P51 OD011132, P30 AI50409, HHSN27201100016C]
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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The goal of an HIV vaccine is to generate robust and durable protective Ab. Vital to this goal is the induction of CD4(+) T follicular helper (T-FH) cells. However, very little is known about the T-FH response to HIV vaccination and its relative contribution to magnitude and quality of vaccine-elicited Ab titers. In this study, we investigated these questions in the context of a DNA/modified vaccinia virus Ankara SIV vaccine with and without gp140 boost in aluminum hydroxide in rhesus macaques. In addition, we determined the frequency of vaccine-induced CD4(+) T cells coexpressing chemokine receptor, CXCR5 (facilitates migration to B cell follicles) in blood and whether these responses were representative of lymph node T-FH responses. We show that booster modified vaccinia virus Ankara immunization induced a distinct and transient accumulation of proliferating CXCR5(+) and CXCR5(-) CD4 T cells in blood at day 7 postimmunization, and the frequency of the former but not the latter correlated with T-FH and B cell responses in germinal centers of the lymph node. Interestingly, gp140 boost induced a skewing toward CXCR3 expression on germinal center T-FH cells, which was strongly associated with longevity, avidity, and neutralization potential of vaccine-elicited Ab response. However, CXCR3(+) cells preferentially expressed the HIV coreceptor CCR5, and vaccine-induced CXCR3(+) CXCR5(+) cells showed a moderate positive association with peak viremia following SIV251 infection. Taken together, our findings demonstrate that vaccine regimens that elicit CXCR3-biased T-FH cell responses favor Ab persistence and avidity but may predispose to higher acute viremia in the event of breakthrough infections.
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