Safety and immunogenicity of a ChAdOx1 vaccine against Rift Valley Fever in adults: an open-label, non-randomised, first-in-human phase 1 clinical trial

BACKGROUND: Rift Valley Fever (RVF) is a viral epidemic illness prevalent in Africa that can be fatal or result in debilitating sequelae in humans. No vaccines are available for human use. We evaluated the safety and immunogenicity of a non-replicating simian adenovirus (ChAdOx1)-vectored RVF vaccine in humans. METHODS: We conducted a phase 1 first-in-human open-label dose-escalation trial in healthy adults in the United Kingdom aged 18 to 55 years (NCT04754776). Participants were non-randomly allocated to receive a single ChAdOx1 RVF vaccination at a dose of either 5×10(9) virus particles (vp), 2·5×10(10) vp or 5×10(10) vp and were followed up for 3 months. The main study objectives were safety and immunogenicity. Primary outcome measures were assessment of adverse events and secondary outcome measures were RVF neutralising antibody titres, RVF GnGc binding antibody titres (ELISA) and cellular response (ELISpot). All participants that received a vaccine were included in analyses. FINDINGS: Between 11(th) June 2021 and 13(th) January 2022, 15 volunteers received a single dose of either 5×10(9) vp (n=3), 2·5×10(10) vp (n=6) or 5×10(10) vp (n=6) ChAdOx1 RVF. ChAdOx1 RVF was well tolerated with no serious adverse events. Adverse events were short lived and predominantly mild. RVF neutralising antibodies (nAb) were detectable across all dose groups, with all vaccinees in the 5×10(10) vp dose group mounting high nAb titres that peaked at day 28 post-vaccination and persisted through the 3 month follow up period. High titres of binding IgG targeting Gc glycoprotein were detected while those targeting Gn were comparatively low. Interferon gamma (IFNγ) cellular responses against RVF Gn and Gc glycoproteins were observed in all but one vaccinee in the 5×10(9) vp dose group. These IFNγ responses peaked at 2 weeks post-vaccination, were highest in the 5×10(10) vp dose group and tended to be more frequent against the Gn glycoprotein. INTERPRETATION: ChAdOx1 RVF vaccine was safe, well-tolerated and immunogenic when administered as a single dose in this study population. The data support further clinical development of ChAdOx1 RVF for human use. FUNDING: UK Department of Health and Social Care through the UK Vaccines Network; Oak Foundation; Wellcome Trust