Codelivery of envelope protein in alum with MVA vaccine induces CXCR3-biased CXCR5+ and CXCR5− CD4 T cell responses in rhesus macaques

SS Iyer, S Gangadhara, B Victor, R Gomez… - The Journal of …, 2015 - journals.aai.org
SS Iyer, S Gangadhara, B Victor, R Gomez, R Basu, JJ Hong, C Labranche, DC Montefiori
The Journal of Immunology, 2015journals.aai.org
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 …
Abstract
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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