Chikungunya virus virus-like particle vaccine safety and immunogenicity in adults older than 65 years: a phase 3, randomised, double-blind, placebo-controlled trial

Abstract

Background: Adults older than 65 years are at increased risk for atypical presentations of chikungunya disease, as well as for severe outcomes including death.

Methods: In this phase 3, randomised, double-blind, placebo-controlled, parallel-group trial, adults aged 65 years and older received a single intramuscular dose of Vimkunya (previously chikungunya virus virus-like particle vaccine) or placebo at ten sites in the USA. Participants, clinical site personnel, and the sponsor were masked to individual treatment assignments until all participants had completed their involvement in the trial and the database was cleaned and locked. Baseline and postvaccination chikungunya virus serum neutralising antibody (SNA) titres (NT₈₀) were assessed at selected timepoints. Safety was assessed up to 183 days after dose administration in all participants from the exposed population who provided safety assessment data. This trial is registered with ClinicalTrials.gov, NCT05349617, and is completed.

Findings: Between May 12 and Dec 2, 2022, 413 participants were recruited and randomly assigned (1:1) to receive the Vimkunya vaccine (n=206) or placebo (n=207). The coprimary endpoints of immunologic superiority of chikungunya virus SNA titres compared with placebo and geometric mean titre at day 22 were met. Vimkunya induced a protective seroresponse (SNA NT₈₀≥100, considered the presumptive seroprotective antibody response) in 149 (82%) of 181 participants (95% CI 76·1-87·2) at day 15, in 165 (87%) of 189 participants (81·8-91·3) at day 22, and in 139 (76%) of 184 participants (68·9-81·2) at day 183. Although there was a slightly higher early immune response in the 65-74 years age group at day 15 compared with the 75 years and older age group, the seroresponse rates at day 22 and day 183 were similar. There were no notable differences in adverse event rates between groups, and most adverse events were grade 1 or 2 in severity and of short duration. No vaccine-related serious adverse events or deaths occurred.

Interpretation: We provide robust data from adults aged 65 years and older showing that Vimkunya is well tolerated and can provide a high rate of protection within 2 weeks postvaccination and during 6 months of follow-up.

Funding: Emergent BioSolutions and Bavarian Nordic.