Vaccine induction of lymph node-resident simian immunodeficiency virus Env-specific T follicular helper cells in rhesus macaques

Diego A. Vargas-Inchaustegui, Andrew Demers, Julia M. Shaw, Guobin Kang, David Ball, Iskra Tuero, Thomas Musich, Venkatramanan Mohanram, Thorsten Demberg, Tatiana S. Karpova, Qingsheng Li, Marjorie Robert-Guroff

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Measurement of Ag-specific T follicular helper (TFH) cell activity in rhesus macaques has not previously been reported. Given that rhesus macaques are the animal model of choice for evaluating protective efficacy of HIV/SIV vaccine candidates and that TFH cells play a pivotal role in aiding B cell maturation, quantifying vaccine induction of HIV/SIV-specific TFH cells would greatly benefit vaccine development. In this study, we quantified SIV Env-specific IL-21-producing TFH cells for the first time, to our knowledge, in a nonhuman primate vaccine study. Macaques were primed twice mucosally with adenovirus 5 host range mutant recombinants encoding SIV Env, Rev, Gag, and Nef followed by two i.m. boosts with monomeric SIV gp120 or oligomeric SIV gp140 proteins. At 2 wk after the second protein boost, we obtained lymph node biopsy specimens and quantified the frequency of total and SIV Env-specific IL-21+ TFH cells and total germinal center B cells, the size and number of germinal centers, and the frequency of SIV-specific Ab-secreting cells in B cell zones. Multiple correlation analyses established the importance of TFH for development of B cell responses in systemic and mucosally localized compartments, including blood, bone marrow, and rectum. Our results suggest that the SIV-specific TFH cells, initially induced by replicating adenovirus-recombinant priming, are long lived. The multiple correlations of SIV Env-specific TFH cells with systemic and mucosal SIV-specific B cell responses indicate that this cell population should be further investigated in HIV vaccine development as a novel correlate of immunity.

Original languageEnglish (US)
Pages (from-to)1700-1710
Number of pages11
JournalJournal of Immunology
Volume196
Issue number4
DOIs
StatePublished - Feb 15 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Vargas-Inchaustegui, D. A., Demers, A., Shaw, J. M., Kang, G., Ball, D., Tuero, I., Musich, T., Mohanram, V., Demberg, T., Karpova, T. S., Li, Q., & Robert-Guroff, M. (2016). Vaccine induction of lymph node-resident simian immunodeficiency virus Env-specific T follicular helper cells in rhesus macaques. Journal of Immunology, 196(4), 1700-1710. https://doi.org/10.4049/jimmunol.1502137