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J Immunol. 2015 Aug 1;195(3):994-1005. doi: 10.4049/jimmunol.1500083. Epub 2015 Jun 26.

Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques.

Author information

1
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329;
2
Department of Surgery, Duke University, Durham, NC 27705;
3
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
4
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; Department of Microbiology and Immunology, Emory University, Atlanta, GA 30329 ramara@emory.edu.

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 (TFH) cells. However, very little is known about the TFH 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 TFH 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 TFH and B cell responses in germinal centers of the lymph node. Interestingly, gp140 boost induced a skewing toward CXCR3 expression on germinal center TFH 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 TFH cell responses favor Ab persistence and avidity but may predispose to higher acute viremia in the event of breakthrough infections.

PMID:
26116502
PMCID:
PMC4506863
DOI:
10.4049/jimmunol.1500083
[Indexed for MEDLINE]
Free PMC Article

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