Sanofi, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France.
Sanofi, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France.
Vaccine. 2022 Aug 5;40(33):4780-4787. doi: 10.1016/j.vaccine.2022.06.040. Epub 2022 Jun 28.
A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a satisfactory safety profile and was immunogenically non-inferior to the licensed purified Vero cell rabies vaccine in adults. Here, we evaluated the safety and immunogenic non-inferiority of PrEP with PVRV-NG compared to the licensed human diploid cell vaccine (HDCV) in healthy adults (NCT01784874). Participants received three vaccinations (days 0, 7, and 28) as PrEP with or without a booster injection after 12 months. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 28 (subgroup only), and 42, and Months 6, 12, and 12 + 14 days (booster group only). Non-inferiority (first primary objective) was based on the proportion of participants with RVNA titres ≥ 0.5 IU/mL (World Health Organization criteria for seroconversion) on day 42, expected to be ≥ 99% (second primary objective). Safety was evaluated after each dose and monitored throughout the study. At day 42, PVRV-NG was non-inferior to HDCV and the first primary objective was met; seroconversion was observed for 98.3% of PVRV-NG recipients and 99.1% of HDCV recipients. As < 99% of participants in the PVRV-NG group had RVNA titres ≥ 0.5 IU/mL, the second primary objective was not met. Booster vaccination produced a strong increase in RVNA titres for all groups, primed with PVRV-NG or HDCV. RVNA geometric mean titres tended to be higher for HDCV than PVRV-NG primary vaccine recipients. In a complementary evaluation using alternative criteria for seroconversion (complete virus neutralization at 1:5 serum dilution), 99.6% and 100% of participants in the PVRV-NG and HDCV groups, respectively, achieved seroconversion across the vaccine groups. No major safety concerns were observed during the study. PVRV-NG was well tolerated, with a similar safety profile to HDCV in terms of incidence, duration, and severity of adverse events after primary and booster vaccinations. ClinicalTrials.gov number: NCT01784874.
一种无血清、高度纯化的 Vero 细胞狂犬病疫苗（PVRV-NG）正在开发中。我们之前的研究表明，PVRV-NG 进行暴露前预防（PrEP）具有令人满意的安全性，在成年人中的免疫原性非劣效于已批准的纯化 Vero 细胞狂犬病疫苗。在此，我们评估了 PVRV-NG 与已批准的人二倍体细胞狂犬病疫苗（HDCV）在健康成年人中的 PrEP 安全性和免疫非劣效性（NCT01784874）。参与者接受三次疫苗接种（第 0、7 和 28 天）作为 PrEP，并在 12 个月后进行加强注射。在第 0、28 天（仅亚组）和 42 天，以及第 6、12 和 12+14 个月（加强组）评估狂犬病病毒中和抗体（RVNA）。非劣效性（第一个主要终点）基于第 42 天 RVNA 滴度≥0.5IU/mL（世界卫生组织的血清转换标准）的参与者比例，预计≥99%（第二个主要终点）。在每次给药后评估安全性，并在整个研究期间进行监测。第 42 天，PVRV-NG 与 HDCV 相比非劣效，并且达到了第一个主要终点；98.3%的 PVRV-NG 受种者和 99.1%的 HDCV 受种者发生血清转换。由于 PVRV-NG 组中<99%的参与者的 RVNA 滴度≥0.5IU/mL，因此未达到第二个主要终点。加强疫苗接种使所有接受 PVRV-NG 或 HDCV 初级疫苗接种的组的 RVNA 滴度显著升高。HDCV 初级疫苗接种者的 RVNA 几何平均滴度往往高于 PVRV-NG。在使用替代血清转换标准（1:5 血清稀释时完全病毒中和）进行的补充评估中，PVRV-NG 组和 HDCV 组的参与者分别有 99.6%和 100%达到血清转换。研究期间未观察到重大安全性问题。PVRV-NG 耐受性良好，与 HDCV 相比，初级和加强疫苗接种后的不良事件发生率、持续时间和严重程度具有相似的安全性特征。临床试验编号：NCT01784874。
