Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial.

"Declaration of interests All authors (except RMa and JLS) are Valneva employees and own stock and share options of Valneva. RH is an inventor in a patent relevant to the work. RMa and JLS are consultants of Valneva and have received payments."

"AcknowledgmentsThis study was funded by Valneva Austria. In addition, we acknowledge the Coalition for Epidemic Preparedness Innovation and EU Horizon 2020 for partially funding the VLA1553 development programme. We thank the independent data safety monitoring board and its members (Herwig Kollaritsch, Lin Chen, Eva-Maria Poellabauer) for their role in this study. We also want to acknowledge the very important contributions made to our VLA1553 programme by Prof Fabrice Simon and Prof Frank Sonnenburg, whose valuable input we will miss greatly. We thank the team at Nexelis, a Q2 Solutions company, especially Luc Gagnon, Julien St-Jean, and Chantal Arguin that did the analysis of neutralising antibodies for this study. Valneva thanks all investigators, site staff, and participants for contributing to this study."

"The study is registered with ClinicalTrials.gov, NCT04546724. Methods: This double-blind, multicentre, randomised, phase 3 trial was done in 43 professional vaccine trial sites in the USA. Eligible participants were healthy volunteers aged 18 years and older. Patients were excluded if they had history of chikungunya virus infection or immune-mediated or chronic arthritis or arthralgia, known or suspected defect of the immune system, any inactivated vaccine received within 2 weeks before vaccination with VLA1553, or any live vaccine received within 4 weeks before vaccination with VLA1553. Participants were randomised (3:1) to receive VLA1553 or placebo. The primary endpoint was the proportion of baseline negative participants with a seroprotective chikungunya virus antibody level defined as 50% plaque reduction in a micro plaque reduction neutralisation test (μPRNT) with a μPRNT50 titre of at least 150, 28 days after vaccination. The safety analysis included all individuals who received vaccination. Immunogenicity analyses were done in a subset of participants at 12 pre-selected study sites. These participants were required to have no major protocol deviations to be included in the per-protocol population for immunogenicity analyses. This trial is registered at ClinicalTrials.gov, NCT04546724."