Vaccines against Lassa fever virus (VITAL): Phase 1 safety and immunogenicity studies of a Lassa fever vaccine, ChAdOx1 LassaJ, in healthy volunteers in the UK and Ghana

Introduction: Lassa fever is a leading cause of viral haemorrhagic fever in West Africa, affecting 59 million people, with up to 500,000 infections and 5,000 deaths annually. Infection during pregnancy poses severe risks to mothers and unborn babies. Survivors may suffer hearing loss or long-term neurological sequelae. No licensed treatment or vaccine exists. ChAdOx1 LassaJ, a simian adenoviral vectored vaccine encoding the Lassa virus glycoprotein, demonstrated immunogenicity and protection from viral challenge preclinically. We will evaluate the safety and immunogenicity of 5×1010vp of ChAdOx1 LassaJ in Phase 1, healthy volunteer trials. Methods: Subject to approvals, healthy adults (18–55 yrs) will be recruited to separate Phase 1 trials in the UK and Ghana. The UK trial will enrol an initial open-label cohort (n=6) receiving two doses of ChAdOx1 LassaJ 12 weeks apart, and a subsequent blinded second cohort (n=20) will be randomised 4:1 to receive 2 doses of ChAdOx1 LassaJ or placebo at a 12-week interval. We anticipate following a similar trial design in Ghana, but the blinded second cohort aims to compare a single dose of ChAdOx1 LassaJ to a prime boost regime, again with a placebo comparator. Safety data from both trials will be reviewed by an independent data and safety monitoring board. Results: Regulatory submissions are underway, and both studies are projected to commence enrolment from Q3 2025. The primary objective is safety and tolerability post vaccination. Secondary objectives include vaccine-induced humoral and cellular immune responses, with assays conducted at both sites. One and two-dose schedule data will inform outbreak and routine immunisation policy in West Africa. Conclusion: These first in-human trials will provide critical data for vaccine development, inform outbreak and routine immunisation policy in West Africa and strengthen research capacity at trial sites.