1. Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial
- Author
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Daniel Jenkin, Adam J Ritchie, Jeremy Aboagye, Sofiya Fedosyuk, Luke Thorley, Samuel Provstgaad-Morys, Helen Sanders, Duncan Bellamy, Rebecca Makinson, Zhi Quan Xiang, Emma Bolam, Richard Tarrant, Fernando Ramos Lopez, Abigail Platt, Ian Poulton, Catherine Green, Hildegund C J Ertl, Katie J Ewer, and Alexander D Douglas
- Subjects
Microbiology (medical) ,Adult ,Infectious Diseases ,Rabies Vaccines ,Rabies ,Virology ,Adenoviruses, Simian ,Humans ,Antibodies, Viral ,Microbiology ,Antibodies, Neutralizing - Abstract
Rabies kills around 60 000 people each year. ChAdOx2 RabG, a simian adenovirus-vectored rabies vaccine candidate, might have potential to provide low-cost single-dose pre-exposure rabies prophylaxis. This first-in-human study aimed to evaluate its safety and immunogenicity in healthy adults.We did a single-centre phase 1 study of ChAdOx2 RabG, administered as a single intramuscular dose, with non-randomised open-label dose escalation at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Healthy adults were sequentially allocated to groups receiving low (5 × 10Between Jan 2 and Oct 28, 2020, 12 adults received low (n=3), middle (n=3), and high doses (n=6) of ChAdOx2 RabG. Participants reported predominantly mild-to-moderate reactogenicity. There were no serious adverse events. Virus neutralising antibody concentrations exceeded the recognised correlate of protection (0·5 IU/mL) in three middle-dose recipients and six high-dose recipients within 56 days of vaccination (median 18·0 IU/mL). The median peak virus neutralising antibody concentrations within 56 days were 0·7 IU/mL (range 0·0-54·0 IU/mL) for the low-dose group, 18·0 IU/mL (0·7-18·0 IU/mL) for the middle-dose group, and 18·0 IU/mL (6·0-486·0 IU/mL) for the high-dose group. Nine participants returned for the additional follow-up after 1 year. Of these nine participants, virus neutralising antibody titres of more than 0·5 IU/mL were maintained in six of seven who had received middle-dose or high-dose ChAdOx2 RabG. Within 7 days of administration of the first dose of a licensed rabies vaccine, nine participants had virus neutralising antibody titres of more than 0·5 IU/mL.In this study, ChAdOx2 RabG showed an acceptable safety and tolerability profile and encouraging immunogenicity, supporting further clinical evaluation.UK Medical Research Council and Engineering and Physical Sciences Research Council.
- Published
- 2022