Pineda-Peña Andrea-Clemencia, Jiang Qian, Petit Celine, Korejwo-Peyramond Joanna, Donazzolo Yves, Latreille Mathilde, Homery Marie-Claude, Babin Valerie, Benamor Sonia, Pichon Sylvie, Guinet-Morlot Françoise, Minutello Ada-Maria
Global Clinical Immunology, Sanofi, Campus Mérieux, Marcy l'Etoile, France.
Patient Safety & Pharmacovigilance, Sanofi, Campus Carteret, Lyon, France.
Clin Infect Dis. 2024 Jun 14;78(6):1748-1756. doi: 10.1093/cid/ciae137.
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®).
This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus 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 PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG 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.
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.
In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines.
NCT03965962.
新一代Vero细胞狂犬病疫苗（PVRV-NG2）是使用与已获许可的纯化Vero细胞疫苗（PVRV；Verorab）和人二倍体细胞疫苗（HDCV；Imovax Rabies®）相同的皮特曼-摩尔毒株研发的。
这项双中心、改良、双盲3期研究评估了在模拟暴露后预防（PEP）方案中，PVRV-NG2联合或不联合肌内注射人狂犬病免疫球蛋白（HRIG）与PVRV + HRIG和HDCV + HRIG相比的免疫原性非劣效性及安全性。18岁及以上的健康成年人（N = 640）按3:1:1:1随机分为PVRV-NG2 + HRIG组、PVRV + HRIG组、HDCV + HRIG组或单独使用PVRV-NG2组（分别于第0天、第3天、第7天、第14天和第28天进行单次疫苗注射，适用组在第0天注射HRIG）。使用快速荧光灶抑制试验在接种疫苗前（第0天）和接种后（第14天、第28天和第42天）评估狂犬病病毒中和抗体（RVNA）滴度。如果PVRV-NG2 + HRIG与PVRV + HRIG/HDCV + HRIG之间比例差异的95%置信区间下限在第28天>-5%，则证明基于达到RVNA滴度≥0.5 IU/mL的参与者比例（主要目标）的非劣效性。在最后一次注射后长达6个月评估安全性。
证明了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%，单独使用PVRV-NG2）在第28天达到RVNA滴度≥0.5 IU/mL。在所有时间点，联合使用HRIG的组之间几何平均滴度相似。PVRV-NG2与对照疫苗的安全性概况相似。
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。
NCT03965962。
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