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Clinical Trial
. 2023 Oct 6;41(42):6309-6317.
doi: 10.1016/j.vaccine.2023.07.046. Epub 2023 Sep 9.

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

Hong-Van Tieu  1 , Shelly Karuna  2 , Yunda Huang  3 , Magdalena E Sobieszczyk  4 , Hua Zheng  2 , Georgia D Tomaras  5 , David C Montefiori  5 , Mingchao Shen  2 , Stephen DeRosa  2 , Kristen Cohen  2 , Margaret Brewinski Isaacs  6 , Stephanie Regenold  7 , Jack Heptinstall  8 , Kelly E Seaton  8 , Sheetal Sawant  8 , Brianna Furch  2 , Michael Pensiero  7 , Lawrence Corey  2 , Katharine J Bar  9 ; HVTN 122 Study Team
Affiliations
Clinical Trial

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

Hong-Van Tieu et al. Vaccine. .

Abstract

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.

Keywords: HIV vaccine; HIV-1; NIH; Phase 1 clinical trial; Subtype C gp145 Env protein; Trimeric envelope protein.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.. HVTN 122 CONSORT diagram.
FU=follow-up, vacc=vaccination, bAb=binding antibody, nAb=neutralizing antibody.
Figure 2.
Figure 2.. Frequency and maximum severity of local and systemic solicited AEs.
A. Local solicited AEs. B. Systemic solicited AEs. There were no instances of vomiting in any treatment arm.
Figure 3.
Figure 3.. IgG binding antibody responses two weeks post last vaccination.
Binding antibody response rates (top graph) and magnitudes (bottom graph) to four different Env antigens. Vaccine given at 300 mcg, turquoise; 100 mcg, orange; placebo, gray. Box plots show median magnitude, 25th and 75th percentile; the whiskers at each end of the box extend to the most extreme data points that are no more than 1.5 times the interquartile range. Positive responders, circles; negative responders, triangles.
Figure 4.
Figure 4.. Neutralizing antibody responses.
nAb response rates (top graph) and magnitudes (bottom graph). Vaccine given at 300 mcg, turquoise; 100 mcg, orange; placebo, gray. Box plots show median magnitude, 25th and 75th percentiles; the whiskers at each end of the box extend to the most extreme data points that are no more than 1.5 times the interquartile range. Positive responders, circles; negative responders, triangles.
Figure 5.
Figure 5.. CD4+ T-cell responses two weeks post last vaccination.
CD4+ T-cell response rates (top graph) and magnitudes (bottom graph) for three antigen peptide pools. Vaccine given at 300 mcg, turquoise; 100 mcg, orange; placebo, gray. Box plots show median magnitude, 25th and 75th percentile; the whiskers at each end of the box extend to the most extreme data points that are no more than 1.5 times the interquartile range. Positive responders, circles; negative responders, triangles.
Figure 6.
Figure 6.. Cross-assay correlation plot.
Antigens tested for each assay (IgG binding antibody, CD4 T cell, or CD8 T cell) are listed. High dose = turquoise; low dose = orange.
See this image and copyright information in PMC

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