Despite availability of effective anti-retroviral drugs, there are still about 38 million people living with HIV-1 infection and about 1.8 million people became newly infected just in 2018. A vaccine is critically needed to stop the AIDS pandemic. Induction of broadly neutralizing antibodies (bnAbs) against HIV-1 is the utmost critical goal towards the development of a protective AIDS vaccine. In this SBIR contract proposal, we will evaluate/optimize a gold nanoparticle (GNP)-based vaccine-delivery platform to elicit bnAbs against the fusion peptide (FP) of HIV-1 gp41. To date, at least three bnAbs have been isolated from HIV-1-infected patients that target the FP and they can neutralize 45-66% of all HIV-1 isolates tested. Developing immunogens and/or establishing vaccine strategies that can induce bnAbs against the FP would be a major milestone towards AIDS vaccine development. In this proposal, we will assess effects of GNP size and shape on antibody responses, determine effects of antigen dosage/density and dose-sparing capacity, evaluate effects of immunization routes, and investigate the influence of different vaccine formulations and regimens that use multiple, antigenically diverse immunogens. Successful completion of this study would overcome a critical roadblock towards development of a protective AIDS vaccine.
