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Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US.

Publication ,  Journal Article
Tieu, H-V; Karuna, S; Huang, Y; Sobieszczyk, ME; Zheng, H; Tomaras, GD; Montefiori, DC; Shen, M; DeRosa, S; Cohen, K; Isaacs, MB; Regenold, S ...
Published in: Vaccine
October 6, 2023

BACKGROUND: An approach to a preventive HIV vaccine is induction of effective broadly neutralizing antibodies (bnAbs) and effector binding antibodies (bAbs). Preclinical studies suggest that trimeric envelope (Env) proteins may elicit nAbs, which led to the development of the recombinant gp145 subtype C Env protein (gp145 C.6980) immunogen. HVTN 122 was a Phase 1 trial that evaluated the safety, tolerability, and immunogenicity of gp145 C.6980 in adults. METHODS: Healthy, HIV-1 seronegative adults received three intramuscular injections of gp145 C.6980 with aluminum hydroxide (alum) at months 0, 2, and 6 at either 300 mcg (high dose, n = 25) or 100 mcg (low dose, n = 15), or placebo/saline (placebo, n = 5). Participants were followed for 12 months. RESULTS: Forty-five participants were enrolled. High and low doses of the study protein were well-tolerated, with mild or moderate reactogenicity commonly reported. Only one adverse event (mild injection site pruritis) in one participant (low dose) was considered product-related; there were no dose-limiting toxicities. High and low dose recipients demonstrated robust bAb responses to vaccine-matched consensus gp140 Env and subtype-matched gp120 Env proteins two weeks post-last vaccination (response rates >90 %), while no responses were detected to a heterologous subtype-matched V1V2 antigen. No significant differences were seen between high and low dose groups. Participants in both experimental arms demonstrated nAb response rates of 76.5 % to a tier 1 virus (MW9635.26), but no responses to tier 2 isolates. Env-specific CD4 + T-cell responses were elicited in 36.4 % of vaccine recipients, without significant differences between groups; no participants demonstrated CD8 + T-cell responses. CONCLUSIONS: Three doses of novel subtype C gp145 Env protein with alum were safe and well-tolerated. Participants demonstrated bAb, Env-specific CD4 + T-cell, and tier 1 nAb responses, but the regimen failed to induce tier 2 or heterologous nAb responses. CLINICAL TRIALS REGISTRATION: NCT03382418.

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Published In

Vaccine

DOI

EISSN

1873-2518

Publication Date

October 6, 2023

Volume

41

Issue

42

Start / End Page

6309 / 6317

Location

Netherlands

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Young Adult
  • Virology
  • Vaccines, Synthetic
  • United States
  • Middle Aged
  • Male
  • Injections, Intramuscular
  • Immunogenicity, Vaccine
  • Humans
 

Citation

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Tieu, H.-V., Karuna, S., Huang, Y., Sobieszczyk, M. E., Zheng, H., Tomaras, G. D., … HVTN 122 Study Team. (2023). Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US. Vaccine, 41(42), 6309–6317. https://doi.org/10.1016/j.vaccine.2023.07.046
Tieu, Hong-Van, Shelly Karuna, Yunda Huang, Magdalena E. Sobieszczyk, Hua Zheng, Georgia D. Tomaras, David C. Montefiori, et al. “Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US.Vaccine 41, no. 42 (October 6, 2023): 6309–17. https://doi.org/10.1016/j.vaccine.2023.07.046.
Tieu, Hong-Van, et al. “Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US.Vaccine, vol. 41, no. 42, Oct. 2023, pp. 6309–17. Pubmed, doi:10.1016/j.vaccine.2023.07.046.
Tieu H-V, Karuna S, Huang Y, Sobieszczyk ME, Zheng H, Tomaras GD, Montefiori DC, Shen M, DeRosa S, Cohen K, Isaacs MB, Regenold S, Heptinstall J, Seaton KE, Sawant S, Furch B, Pensiero M, Corey L, Bar KJ, HVTN 122 Study Team. Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US. Vaccine. 2023 Oct 6;41(42):6309–6317.
Journal cover image

Published In

Vaccine

DOI

EISSN

1873-2518

Publication Date

October 6, 2023

Volume

41

Issue

42

Start / End Page

6309 / 6317

Location

Netherlands

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Young Adult
  • Virology
  • Vaccines, Synthetic
  • United States
  • Middle Aged
  • Male
  • Injections, Intramuscular
  • Immunogenicity, Vaccine
  • Humans