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Single-Visit Rabies Vaccination as Pre-Exposure Prophylaxis Induces a Rapid and Effective Anamnestic Antibody Response: A Randomised Controlled Non-Inferiority Trial
24 Pages Posted: 11 May 2023More...
Background: After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). PrEP is not sufficiently accessible as it is cost- and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing these barriers.
Methods: In a randomised controlled, multicentre non-inferiority trial (EudraCT: 2017-000089-31), 288 participants were randomised to (A) single-visit intramuscular (1·0 mL); (B) single-visit intradermal (0·2 mL); (C) standard two-visit intramuscular (1·0 mL; day 0 and 7) PrEP; or (D) no rabies vaccination. Six months later, participants received simulated intramuscular rabies PEP (1·0 mL; day 0 and 3). Rabies virus neutralising antibody (RVNA) concentrations were measured repeatedly. The primary outcome was the fold increase in geometric mean RVNA concentrations between day 0 and 7 after simulated PEP. The non-inferiority margin was 0·67.
Findings: 214 participants (aged 18-50) were evaluated for the primary outcome. Single-visit intramuscular rabies PrEP induced an anamnestic antibody response non-inferior compared with the two-visit intramuscular schedule, single-visit intradermal PrEP did not. The fold increase in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43, 3·77]) and 1·11 (95% CI [0·66, 1·87]) times as high as the fold increase in the standard schedule, respectively. Seroconversion rates (RVNA concentration ≥ 0·5 IU/mL) seven days after PEP were 100% in the intramuscular groups, 96% in the intradermal group, and 15% in the group without PrEP.
Interpretation: Single intramuscular rabies vaccination can effectively prime adults (aged 18-50).
Trial Registration: Registered in the Dutch Trial registry (NTR6817) and in EudraCT (2017-000089-31).
Funding: ZonMW funded this study (grant: 522003008).
Declaration of Interest: LAO and LGV are currently conducting a study sponsored by Bavarian Nordic, the manufacturer of Rabipur vaccine. Bavarian Nordic had no role in designing, conducting, analysing or reporting the trial on which this manuscript reports. All other authors declare no competing interests.
Ethical Approval: The study was conducted in line with the ICH guidelines for Good Clinical Practice and the Declaration of Helsinki. Informed consent was obtained from participants before any study procedure was performed. Ethics approval was obtained from an independent ethics committee (Stichting Bebo, NL60550.056.17).
Keywords: Rabies, vaccination, neglected tropical diseases, pre-exposure prophylaxis, single-visit, intramuscular, intradermal
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