Boostability after single-visit pre-exposure prophylaxis with rabies vaccine: a randomised controlled non-inferiority trial

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Pubblicato in:The Lancet Infectious Diseases vol. 24, no. 2 (Feb 2024), p. 206
Autore principale: Overduin, Lisanne A
Altri autori: Koopman, Jan Pieter R, Prins, Corine, Verbeek-Menken, Petra H, De Pijper, Cornelis A, Eblé, Phaedra L, Heerink, Fiona, Perry J J van Genderen, Grobusch, Martin P, Visser, Leo G
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100 1 |a Overduin, Lisanne A  |u Department of Infectious Diseases, Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands 
245 1 |a Boostability after single-visit pre-exposure prophylaxis with rabies vaccine: a randomised controlled non-inferiority trial 
260 |b Elsevier Limited  |c Feb 2024 
513 |a Evidence Based Healthcare Journal Article 
520 3 |a Summary Background After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). However, PrEP is not sufficiently accessible as it is cost-intensive and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing some of these barriers. Methods In a block-randomised (2:2:2:1) controlled, multicentre non-inferiority trial, healthy adult travellers (aged 18–50 years and >50 years) were randomly assigned 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. 6 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 for all participants. The two main comparisons of this primary outcome are between the standard two-visit schedule and the one-visit intramuscular schedule, and between the standard two-visit schedule and the one-visit intradermal schedule. The non-inferiority margin was 0·67. This study is registered with EudraCT, 2017-000089-31. Findings Between May 16, 2018, and March 26, 2020, 288 healthy adult travellers were randomly assigned and 214 participants 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 increases in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43–3·77]) and 1·11 (0·66–1·87) times as high as the fold increase in the standard schedule, respectively. No vaccine-related serious adverse events were observed. Adverse events related to vaccination were mostly mild. Interpretation Single intramuscular rabies vaccination can effectively prime travellers (aged 18–50 years), and potentially other populations, and could replace current standard two-visit rabies vaccination as PrEP. Funding ZonMW. Translation For the Dutch translation of the abstract see Supplementary Materials section. 
653 |a Antibodies 
653 |a Vaccines 
653 |a Animals 
653 |a Rabies 
653 |a Antibody response 
653 |a Disease prevention 
653 |a Immunoglobulins 
653 |a Bats 
653 |a Translation 
653 |a Costs 
653 |a Exposure 
653 |a Travellers 
653 |a Age groups 
653 |a Schedules 
653 |a Antiretroviral drugs 
653 |a Lyssavirus 
653 |a Social 
700 1 |a Koopman, Jan Pieter R  |u Department of Infectious Diseases, Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands 
700 1 |a Prins, Corine  |u Department of Infectious Diseases, Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands 
700 1 |a Verbeek-Menken, Petra H  |u Department of Infectious Diseases, Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands 
700 1 |a De Pijper, Cornelis A  |u Centre for Tropical Medicine and Travel Medicine, Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, Netherlands 
700 1 |a Eblé, Phaedra L  |u Wageningen Bioveterinary Research, Lelystad, Netherlands 
700 1 |a Heerink, Fiona  |u Department of Infectious Diseases, Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands 
700 1 |a Perry J J van Genderen  |u Corporate Travel Clinic, Erasmus Medical Centre, Rotterdam, Netherlands 
700 1 |a Grobusch, Martin P  |u Centre for Tropical Medicine and Travel Medicine, Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, Netherlands 
700 1 |a Visser, Leo G  |u Department of Infectious Diseases, Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands 
773 0 |t The Lancet Infectious Diseases  |g vol. 24, no. 2 (Feb 2024), p. 206 
786 0 |d ProQuest  |t Health & Medical Collection 
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