在中国健康、未感染 HIV-1 的成年参与者中评估一种重组寡聚 gp145 亚型 C Env 蛋白（gp145 C.6980）HIV 候选疫苗的安全性和免疫原性。
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.
机构信息
Laboratory of Infectious Disease Prevention, Lindsley F. Kimball Research Institute, New York Blood Center, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
出版信息
Vaccine. 2023 Oct 6;41(42):6309-6317. doi: 10.1016/j.vaccine.2023.07.046. Epub 2023 Sep 9.
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.
背景
预防 HIV 疫苗的方法是诱导有效的广泛中和抗体（bnAbs）和效应结合抗体（bAbs）。临床前研究表明，三聚体包膜（Env）蛋白可能引发 nAbs，这导致了重组 gp145 亚 C 型 Env 蛋白（gp145 C.6980）免疫原的开发。HVTN 122 是一项评估 gp145 C.6980 在成年人中的安全性、耐受性和免疫原性的 1 期试验。
方法
健康、HIV-1 血清阴性的成年人在 0、2 和 6 个月时分别接受三种含铝佐剂的 gp145 C.6980 肌内注射，剂量分别为 300 mcg（高剂量，n=25）或 100 mcg（低剂量，n=15），或安慰剂/生理盐水（安慰剂，n=5）。参与者随访 12 个月。
结果
共纳入 45 名参与者。研究蛋白的高剂量和低剂量均耐受良好，通常报告有轻度或中度的反应原性。只有一名参与者（低剂量）的 1 例不良事件（轻度注射部位瘙痒）被认为与产品有关；没有剂量限制毒性。高剂量和低剂量组在最后一次接种后两周均能检测到针对疫苗匹配的共识 gp140 Env 和亚型匹配的 gp120 Env 蛋白的 bAb 反应（反应率>90%），而对异源亚型匹配的 V1V2 抗原无反应。高剂量和低剂量组之间无显著差异。两组实验臂的参与者对 tier 1 病毒（MW9635.26）的 nAb 反应率均为 76.5%，但对 tier 2 分离物无反应。在 36.4%的疫苗接种者中检测到 Env 特异性 CD4+T 细胞反应，各组之间无显著差异；无参与者表现出 CD8+T 细胞反应。
结论
三剂新型 C 型 gp145 Env 蛋白与铝佐剂联合使用是安全且耐受良好的。参与者表现出 bAb、Env 特异性 CD4+T 细胞和 tier 1 nAb 反应，但该方案未能诱导 tier 2 或异源 nAb 反应。
临床试验注册
NCT03382418。
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