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

• Published in: The Lancet infectious diseases 2023-08, Vol.23 (8), p.956-964
• Main Authors: Jenkin, Daniel, Wright, Daniel, Folegatti, Pedro M, Platt, Abigail, Poulton, Ian, Lawrie, Alison, Tran, Nguyen, Boyd, Amy, Turner, Cheryl, Gitonga, John N, Karanja, Henry K, Mugo, Daisy, Ewer, Katie J, Bowden, Thomas A, Gilbert, Sarah C, Charleston, Bryan, Kaleebu, Pontiano, Hill, Adrian V S, Warimwe, George M
• Format: Article
• Language: English
• Subjects: Adenoviruses; Adult; Adults; Adverse events; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Binding; Cattle; Clinical trials; Coccidioidomycosis; Comorbidity; Complications; COVID-19 vaccines; Disease transmission; Double-Blind Method; Enzyme-linked immunosorbent assay; Epidemics; Female; Fever; Gastrointestinal symptoms; Glycoproteins; Headache; Health care; Humans; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Infectious diseases; Leukocytes (neutrophilic); Livestock; Lymphocytes; Lymphopenia; Male; Population studies; Regulatory approval; Research ethics; Rift Valley fever; Rift Valley Fever - prevention & control; Safety; Sheep; Translation; United Kingdom; Vaccines; Vector-borne diseases; Viral diseases; Viral Vaccines; γ-Interferon
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(23)00068-3

Rift Valley fever 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 aimed to evaluate the safety and immunogenicity of a non-replicating simian adenovirus-vectored Rift Valley fever (ChAdOx1 RVF) vaccine in humans. We conducted a phase 1, first-in-human, open-label, dose-escalation trial in healthy adults aged 18–50 years at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Participants were required to have no serious comorbidities or previous history of receiving an adenovirus-based vaccine before enrolment. Participants were non-randomly allocated to receive a single ChAdOx1 RVF dose of either 5 × 109 virus particles (vp), 2·5 × 1010 vp, or 5 × 1010 vp administered intramuscularly into the deltoid of their non-dominant arm; enrolment was sequential and administration was staggered to allow for safety to be assessed before progression to the next dose. Primary outcome measures were assessment of adverse events and secondary outcome measures were Rift Valley fever neutralising antibody titres, Rift Valley fever GnGc-binding antibody titres (ELISA), and cellular response (ELISpot), analysed in all participants who received a vaccine. This trial is registered with ClinicalTrials.gov (NCT04754776). Between June 11, 2021, and Jan 13, 2022, 15 volunteers received a single dose of either 5 × 109 vp (n=3), 2·5 × 1010 vp (n=6), or 5 × 1010 vp (n=6) ChAdOx1 RVF. Nine participants were female and six were male. 14 (93%) of 15 participants reported solicited local adverse reactions; injection-site pain was the most frequent (13 [87%] of 15). Ten (67%) of 15 participants (from the 2·5 × 1010 vp and 5 × 1010 vp groups only) reported systemic symptoms, which were mostly mild in intensity, the most common being headache (nine [60%] of 15) and fatigue (seven [47%]). All unsolicited adverse events reported within 28 days were either mild or moderate in severity; gastrointestinal symptoms were the most common reaction (at least possibly related to vaccination), occurring in four (27%) of 15 participants. Transient decreases in total white cell, lymphocyte, or neutrophil counts occurred at day 2 in some participants in the intermediate-dose and high-dose groups. Lymphopenia graded as severe occurred in two participants in the 5 × 1010 vp group at a single timepoint, but resolved at the subsequent follow-up visit. No serious adverse events occurred.