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Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.

Publication ,  Journal Article
Chua, JV; Davis, C; Husson, JS; Nelson, A; Prado, I; Flinko, R; Lam, KWJ; Mutumbi, L; Mayer, BT; Dong, D; Fulp, W; Mahoney, C; Gerber, M ...
Published in: Vaccine
June 29, 2021

A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant. We enrolled 65 healthy adult volunteers in this first-in-human phase 1a randomized, double-blind, placebo-controlled study with three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. The overall incidence of adverse events (AEs) was not significantly different between vaccinees and controls. The majority (89%) of vaccine-related AE were mild. The most common vaccine-related adverse event was injection site pain. There were no vaccine-related serious AE, discontinuation due to AE, intercurrent HIV infection, or significant decreases in CD4 count. By the final vaccination, all vaccine recipients developed antibodies against IHV01 and demonstrated anti-CD4i epitope antibodies. The elicited antibodies reacted with CD4 non-liganded Env antigens from diverse HIV-1 strains. Antibody-dependent cell-mediated cytotoxicity against heterologous infected cells or gp120 bound to CD4+ cells was evident in all cohorts as were anti-gp120 T-cell responses. IHV01 vaccine was safe, well tolerated, and immunogenic at all doses tested. The vaccine raised broadly reactive humoral responses against conserved CD4i epitopes on gp120 that mediates antiviral functions.

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Published In

Vaccine

DOI

EISSN

1873-2518

Publication Date

June 29, 2021

Volume

39

Issue

29

Start / End Page

3879 / 3891

Location

Netherlands

Related Subject Headings

  • Virology
  • Vaccines, Subunit
  • Immunogenicity, Vaccine
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • CD4 Antigens
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chua, J. V., Davis, C., Husson, J. S., Nelson, A., Prado, I., Flinko, R., … Sajadi, M. M. (2021). Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial. Vaccine, 39(29), 3879–3891. https://doi.org/10.1016/j.vaccine.2021.05.090
Chua, Joel V., Charles Davis, Jennifer S. Husson, Amy Nelson, Ilia Prado, Robin Flinko, Ka Wing J. Lam, et al. “Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.Vaccine 39, no. 29 (June 29, 2021): 3879–91. https://doi.org/10.1016/j.vaccine.2021.05.090.
Chua JV, Davis C, Husson JS, Nelson A, Prado I, Flinko R, et al. Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial. Vaccine. 2021 Jun 29;39(29):3879–91.
Chua, Joel V., et al. “Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.Vaccine, vol. 39, no. 29, June 2021, pp. 3879–91. Pubmed, doi:10.1016/j.vaccine.2021.05.090.
Chua JV, Davis C, Husson JS, Nelson A, Prado I, Flinko R, Lam KWJ, Mutumbi L, Mayer BT, Dong D, Fulp W, Mahoney C, Gerber M, Gottardo R, Gilliam BL, Greene K, Gao H, Yates N, Ferrari G, Tomaras G, Montefiori D, Schwartz JA, Fouts T, DeVico AL, Lewis GK, Gallo RC, Sajadi MM. Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial. Vaccine. 2021 Jun 29;39(29):3879–3891.
Journal cover image

Published In

Vaccine

DOI

EISSN

1873-2518

Publication Date

June 29, 2021

Volume

39

Issue

29

Start / End Page

3879 / 3891

Location

Netherlands

Related Subject Headings

  • Virology
  • Vaccines, Subunit
  • Immunogenicity, Vaccine
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • CD4 Antigens
  • Animals