Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

Publication Type:

Journal Article

Source:

Clinical and vaccine immunology : CVI, Volume 23, Issue 6, p.496-506 (2016)

Abstract:

BACKGROUND: A Phase I safety and immunogenicity study investigated SAAVI HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with Modified Vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in RV144, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. METHODS: 48 participants (12 USA; 36 RSA) were randomized to receive 3 intramuscular (IM) doses of SAAVI DNA-C2 4 mg (months 0, 1, 2) and 2 IM doses of SAAVI MVA-C 1.45x10(9)pfu (months 4, 5) (n=40) or placebo (n=8). Approximately two years after vaccination, 27 participants were re-randomized to receive gp140/MF59 100 mcg or placebo, as 2 IM injections, 3 months apart. RESULTS: The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen CD4+T-cell and CD8+T cell responses occurred in 74% and 32% of participants respectively. The protein boost increased CD4+T-cell responses to 87% of subjects. All participants developed Tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. CONCLUSION: The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced binding and neutralizing antibodies as well as CD4(+)T-cell responses to HIV-1 envelope.Trial registration numbers: NCT00574600; NCT01423825;https://clinicaltrials.gov/ct2/show/NCT00574600?term=hvtn+073&rank=2)https://clinicaltrials.gov/ct2/show/NCT01423825?term=hvtn+073&rank=1).