Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques.

Journal Article (Journal Article)

UNLABELLED: The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test whether triggering multiple pathogen-associated molecular pattern receptors could enhance immunogenicity. Compared to single TLR agonists or other pairwise combinations, TLR7/8 and TLR9 agonists combined were able to elicit the highest titers of binding, neutralizing, and antibody-dependent cellular cytotoxicity-mediating antibodies against the protein immunogen, transmitted/founder HIV-1 envelope gp140 (B.63521). We further found that the combination of TLR7/8 and TLR9 agonists was associated with the release of CXCL10 (IP-10), suggesting that this adjuvant formulation may have optimally stimulated innate and adaptive immunity to elicit high titers of antibodies. IMPORTANCE: Combining TLR agonists in an adjuvant formulation resulted in higher antibody levels compared to an adjuvant without TLR agonists. Adjuvants that combine TLR agonists may be useful for enhancing antibody responses to HIV-1 vaccines.

Full Text

Duke Authors

Cited Authors

  • Moody, MA; Santra, S; Vandergrift, NA; Sutherland, LL; Gurley, TC; Drinker, MS; Allen, AA; Xia, S-M; Meyerhoff, RR; Parks, R; Lloyd, KE; Easterhoff, D; Alam, SM; Liao, H-X; Ward, BM; Ferrari, G; Montefiori, DC; Tomaras, GD; Seder, RA; Letvin, NL; Haynes, BF

Published Date

  • March 2014

Published In

Volume / Issue

  • 88 / 6

Start / End Page

  • 3329 - 3339

PubMed ID

  • 24390332

Pubmed Central ID

  • PMC3957956

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.03309-13


  • eng

Conference Location

  • United States