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.

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.).

• Authors: Glenda E Gray, Kenneth H Mayer, Marnie L Elizaga, Linda-Gail Bekker, Mary Allen, Lynn Morris, David Montefiori, Stephen C De Rosa, Alicia Sato, Niya Gu, Georgia D Tomaras, Timothy Tucker, Susan W Barnett, Nonhlanhla N Mkhize, Xiaoying Shen, Katrina Downing, Carolyn Williamson, Michael Pensiero, Lawrence Corey, Anna-Lise Williamson
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 23 Issue 6 Pg. 496-506 (06 2016) ISSN: 1556-679X [Electronic] United States
• PMID: 27098021 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Gray et al.

Chemical References

• AIDS Vaccines
• Antibodies, Neutralizing
• HIV Antibodies
• Vaccines, DNA
• env Gene Products, Human Immunodeficiency Virus
• gp140 envelope protein, Human immunodeficiency virus 1

Topics

• AIDS Vaccines (administration & dosage, classification, immunology)
• Acquired Immunodeficiency Syndrome (prevention & control)
• Adolescent
• Adult
• Antibodies, Neutralizing (blood)
• CD4 Lymphocyte Count
• Enzyme-Linked Immunospot Assay
• Female
• HIV Antibodies (blood, immunology)
• HIV-1 (immunology)
• Humans
• Immunity, Cellular
• Immunization Schedule
• Immunization, Secondary (adverse effects)
• Injections, Intramuscular
• Male
• South Africa
• Time Factors
• Vaccination
• Vaccines, DNA (administration & dosage, immunology)
• Vaccinia (genetics, immunology)
• Young Adult
• env Gene Products, Human Immunodeficiency Virus (administration & dosage, immunology)