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.

Published

Journal Article

A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (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 the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. 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 the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the 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. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.).

Full Text

Duke Authors

Cited Authors

  • Gray, GE; Mayer, KH; Elizaga, ML; Bekker, L-G; Allen, M; Morris, L; Montefiori, D; De Rosa, SC; Sato, A; Gu, N; Tomaras, GD; Tucker, T; Barnett, SW; Mkhize, NN; Shen, X; Downing, K; Williamson, C; Pensiero, M; Corey, L; Williamson, A-L

Published Date

  • June 6, 2016

Published In

Volume / Issue

  • 23 / 6

Start / End Page

  • 496 - 506

PubMed ID

  • 27098021

Pubmed Central ID

  • 27098021

Electronic International Standard Serial Number (EISSN)

  • 1556-679X

International Standard Serial Number (ISSN)

  • 1556-6811

Digital Object Identifier (DOI)

  • 10.1128/CVI.00717-15

Language

  • eng