Toll-like Receptor 7/8 (TLR7/8) and TLR9 Agonists Cooperate to Enhance HIV-1 Envelope Antibody Responses in Rhesus Macaques

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2014 Jan 7

PMID 24390332

Citations 57

Authors

M Anthony Moody

Sampa Santra

Nathan A Vandergrift

Laura L Sutherland

Thaddeus C Gurley

Mark S Drinker

Ashley A Allen

Shi-Mao Xia

R Ryan Meyerhoff

Robert Parks

Krissey E Lloyd

David Easterhoff

S Munir Alam

Hua-Xin Liao

Brandy M Ward

Guido Ferrari

David C Montefiori

Georgia D Tomaras

Robert A Seder

Norman L Letvin

Barton F Haynes

Affiliations

Soon will be listed here.

Abstract

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.

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