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Clin Vaccine Immunol. 2016 Jun 6;23(6):496-506. doi: 10.1128/CVI.00717-15. Print 2016 Jun.

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.

Author information

1
Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Glenda.gray@mrc.ac.za.
2
South African Medical Research Council, Cape Town, South Africa.
3
Fenway Health and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
4
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
5
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
6
DAIDS, NIAID, NIH, Washington, DC, USA.
7
National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
8
Duke University, Durham, North Carolina, USA.
9
Novartis Vaccines, Cambridge, Massachusetts, USA.
10
National Health Laboratory Service, Cape Town, South Africa.

Abstract

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.).

PMID:
27098021
PMCID:
PMC4895009
DOI:
10.1128/CVI.00717-15
[Indexed for MEDLINE]
Free PMC Article

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