Codelivery of envelope protein in alum with MVA vaccine induces CXCR3-biased CXCR5+ and CXCR5− CD4 T cell responses in rhesus macaques
The Journal of Immunology, 2015•journals.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 …
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.
journals.aai.org