Background A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab®) and the human diploid cell vaccine (HDCV; Imovax Rabies®). Methods This dual-center, modified double-blind, phase III study in France evaluated immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG), compared with PVRV+HRIG and HDCV+HRIG, in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N=640) were randomized 3:1:1:1 to receive PVRV-NG2+HRIG, PVRV+HRIG, HDCV+HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, 3, 7, 14, and 28, with HRIG administered on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA titers) were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2+HRIG and PVRV+HRIG/HDCV+HRIG was >−5% at D28. Safety was assessed up to 6 months after the last injection. Results The non-inferiority of PVRV-NG2+HRIG, compared with PVRV+HRIG and HDCV+HRIG, was demonstrated. Nearly all participants (99.6%, PVRV-NG2+HRIG; 100%, PVRV+HRIG; 98.7%, HDCV+HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. Conclusions In a simulated PEP setting, PVRV-NG2+HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. Clinical Trials Registration NCT03965962.

中文翻译：

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纯化 Vero 狂犬病疫苗（无血清）的免疫原性和安全性，与两种许可的疫苗相比，在法国健康成年人中模拟狂犬病暴露后方案：随机对照 III 期试验

背景 下一代 Vero 细胞狂犬病疫苗 (PVRV-NG2) 是使用与许可的纯化 Vero 细胞疫苗（PVRV；Verorab®）和人二倍体细胞疫苗（HDCV；Imovax Rabies®）相同的 Pitman-Moore 菌株开发的。方法 这项在法国进行的双中心、改良双盲 III 期研究评估了与 PVRV+HRIG 和 HDCV+HRIG 相比，PVRV-NG2 在联合或不联合肌肉注射人狂犬病免疫球蛋白 (HRIG) 的情况下的免疫原性非劣效性和安全性。模拟暴露后预防（PEP）方案。≥18 岁的健康成年人 (N=640) 按 3:1:1:1 随机分配接受 PVRV-NG2+HRIG、PVRV+HRIG、HDCV+HRIG 或单独的 PVRV-NG2（在 [[] 日进行单次疫苗注射） D] 0、3、7、14 和 28，在适用组中 D0 时施用 HRIG）。使用快速荧光焦点抑制试验评估疫苗接种前（D0）和疫苗后（D14、D28 和 D42）狂犬病病毒中和抗体（RVNA 滴度）。根据达到 RVNA 滴度≥0.5 IU/mL（主要目标）的参与者比例，如果 PVRV-NG2+HRIG 和 PVRV+HRIG/ 之间比例差异的 95% CI 下限被证明为非劣效性D28时HDCV+HRIG＞-5％。最后一次注射后 6 个月内评估安全性。结果 PVRV-NG2+HRIG 与 PVRV+HRIG 和 HDCV+HRIG 相比具有非劣效性。几乎所有参与者（99.6%，PVRV-NG2+HRIG；100%，PVRV+HRIG；98.7%，HDCV+HRIG；100%，单独PVRV-NG2）在第28天时RVNA滴度≥0.5 IU/mL。在所有时间点同时给予 HRIG 的组之间的几何平均滴度相似。PVRV-NG2 和对照疫苗的安全性相似。结论 在模拟 PEP 环境中，PVRV-NG2+HRIG 显示出与当前标准护理疫苗相当的免疫原性和安全性。临床试验注册NCT03965962。