Journal
JOURNAL OF VIROLOGY
Volume 88, Issue 6, Pages 3329-3339Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.03309-13
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Funding
- Collaboration for AIDS Vaccine Discovery grant
- Bill and Melinda Gates Foundation
- Center For HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]
- Center For HIV/AIDS Vaccine Immunology-Immunogen Discovery grant (CHAVI-ID) [UM1 AI100645]
- CAVD funding for the CTVIMC, grant [OPP1032325]
- Duke University Center for AIDS Research Flow Cytometry and Virology cores (CFAR) [P30-AI-64518]
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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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