Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: A randomised phase II pre-exposure prophylaxis study.

Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE

Publication: Amsterdam, The Netherlands : Elsevier Science
Original Publication: [Guildford, Surrey, UK] : Butterworths, [c1983-

Rabies*/prevention & control ; Rabies Vaccines*/adverse effects ; Rabies Vaccines*/immunology; Adult ; Antibodies, Viral ; Humans ; Pre-Exposure Prophylaxis ; Rabies virus

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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SP, AMM, AM, CP, and FGM are Sanofi employees and may hold shares and/or stock options in the company.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Keywords: Booster vaccination; Human diploid cell vaccine; Pre-exposure prophylaxis; Rabies; Serum free; Vero cell rabies vaccine

ClinicalTrials.gov NCT01784874

0 (Antibodies, Viral)
0 (Rabies Vaccines)

Date Created: 20220701 Date Completed: 20220816 Latest Revision: 20220921

20240105

10.1016/j.vaccine.2022.06.040

35778281