Polyinosinic-polycytidylic acid is the most effective TLR adjuvant for SIV gag protein-induced t cell responses in nonhuman primates

Haesun Park, Lauren Adamson, Tae Ha, Karl Mullen, Shoko I. Hagen, Arys Nogueron, Andrew W. Sylwester, Michael K. Axthelm, Al Legasse, Michael Piatak, Jeffrey D. Lifson, Juliana M. McElrath, Louis J. Picker, Robert A. Seder

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Prime-boost immunization with heterologous vaccines elicits potent cellular immunity. In this study, we assessed the influence of various TLR ligands on SIV Gag-specific T cell immunity and protection following prime-boost immunization. Rhesus macaques (RMs) were primed with SIV Gag protein emulsified in Montanide ISA51 with or without TLR3 (polyinosinic-polycytidylic acid [poly-IC]), TLR4 (monophosphoryl lipid A), TLR7/8 (3M-012), TLR9 (CpG), or TLR3 (poly-IC) combined with TLR7/8 ligands, then boosted with replication defective adenovirus 5 expressing SIV Gag (rAd5-Gag). After priming, RMs that received SIV Gag protein plus poly-IC developed significantly higher frequencies of SIV Gag-specific CD4+ Th1 responses in blood and bronchoal-veolar lavage (BAL) fluid lymphocytes compared with all other adjuvants, and low-level SIV Gag-specific CD8+ T cell responses. After the rAd5-Gag boost, the magnitude and breadth of SIV Gag-specific CD8+ T cell responses were significantly increased in RM primed with SIV Gag protein plus poly-IC, with or without the TLR7/8 ligand, or CpG. However, the anamnestic, SIV Gag-specific CD8+ T cell response to SIVmac251 challenge was not significantly enhanced by SIV Gag protein priming with any of the adjuvants. In contrast, the anamnestic SIV Gag-specific CD4+ T cell response in BAL was enhanced by SIV Gag protein priming with poly-IC or CpG, which correlated with partial control of early viral replication after SIVmac251 challenge. These results demonstrate that prime-boost vaccination with SIV Gag protein/poly-IC improves magnitude, breadth, and durability of CD4+ T cell immune responses, which could have a role in the control of SIV viral replication.

Original languageEnglish (US)
Pages (from-to)4103-4115
Number of pages13
JournalJournal of Immunology
Volume190
Issue number8
DOIs
StatePublished - Apr 15 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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