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

Publication ,  Journal Article
Iyer, SS; Gangadhara, S; Victor, B; Gomez, R; Basu, R; Hong, JJ; Labranche, C; Montefiori, DC; Villinger, F; Moss, B; Amara, RR
Published in: J Immunol
August 1, 2015

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.

Duke Scholars

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

August 1, 2015

Volume

195

Issue

3

Start / End Page

994 / 1005

Location

United States

Related Subject Headings

  • Viremia
  • Viral Vaccines
  • Viral Load
  • Viral Envelope Proteins
  • Vaccines, DNA
  • Vaccination
  • T-Lymphocytes, Helper-Inducer
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Receptors, CXCR5
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Iyer, S. S., Gangadhara, S., Victor, B., Gomez, R., Basu, R., Hong, J. J., … Amara, R. R. (2015). Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques. J Immunol, 195(3), 994–1005. https://doi.org/10.4049/jimmunol.1500083
Iyer, Smita S., Sailaja Gangadhara, Blandine Victor, Rosy Gomez, Rahul Basu, Jung Joo Hong, Celia Labranche, et al. “Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques.J Immunol 195, no. 3 (August 1, 2015): 994–1005. https://doi.org/10.4049/jimmunol.1500083.
Iyer SS, Gangadhara S, Victor B, Gomez R, Basu R, Hong JJ, et al. Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques. J Immunol. 2015 Aug 1;195(3):994–1005.
Iyer, Smita S., et al. “Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques.J Immunol, vol. 195, no. 3, Aug. 2015, pp. 994–1005. Pubmed, doi:10.4049/jimmunol.1500083.
Iyer SS, Gangadhara S, Victor B, Gomez R, Basu R, Hong JJ, Labranche C, Montefiori DC, Villinger F, Moss B, Amara RR. Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques. J Immunol. 2015 Aug 1;195(3):994–1005.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

August 1, 2015

Volume

195

Issue

3

Start / End Page

994 / 1005

Location

United States

Related Subject Headings

  • Viremia
  • Viral Vaccines
  • Viral Load
  • Viral Envelope Proteins
  • Vaccines, DNA
  • Vaccination
  • T-Lymphocytes, Helper-Inducer
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Receptors, CXCR5