#Safety and immunogenicity of a live-attenuated #chikungunya virus #vaccine in #adolescents: final results from a ... phase 3 trial in endemic areas of #Brazil

Summary

Background

Chikungunya outbreaks have recurred in Brazil since 2014. Building on earlier 28-day post-vaccination data, we now report 12-month safety and immunogenicity results of the VLA1553 vaccine in Brazilian adolescents.

Methods

In this double-blind, randomised, placebo-controlled, phase 3 trial, generally healthy adolescents aged 12–17 years were recruited at ten sites across Brazil. Individuals were excluded for immune-mediated or chronic arthritis or arthralgia, who are are immunologically compromised, or any recent live vaccines. Random allocation via simple block randomisation in a 2:1 ratio was stratified by baseline IgG and IgM serostatus by ELISA to receive a single intramuscular dose of VLA1553 or placebo. Assessed in the per-protocol population 28 days after vaccination, the primary endpoint was the proportion of baseline seronegative participants with chikungunya virus neutralising antibody levels assessed by a serum dilution achieving a 50% plaque reduction in a micro plaque reduction neutralisation test with a titre of 150 or more, an accepted surrogate of protection. Safety was assessed in all vaccinated participants and covered by several secondary trial endpoints; immunogenicity formed a prespecified subset for analysis. The trial is registered with ClinicalTrials.gov (NCT04650399) and is complete.

Findings

Between Feb 14, 2022, and Feb 16, 2024, 754 participants were vaccinated (502 [67%] with VLA1553 and 252 [33%] with placebo), with a per-protocol population of 351 participants for immunogenicity analyses (303 in the VLA1553 group and 48 in the placebo group). 406 (54%) of all participants were female and 348 (46%) participants were male; the median age was 15·0 years, and the majority of participants were White (245 [33%]), followed by 214 (28%) other and 192 (26%) multiracial. In baseline seronegative participants, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 248 of 251 participants (98·8% [95% CI 96·5–99·8]) 28 days after vaccination, which was sustained in 232 of 236 participants (98·3% [95·7–99·5]) at 12 months post-vaccination. VLA1553 was generally well tolerated, with the vast majority (2082 [97%] of 2155) of adverse events of mild or moderate intensity. When compared with placebo, participants exposed to VLA1553 had a significantly higher frequency of related adverse events (352 [70%] of 502 vs 122 [48%] of 252; p<0·0001), mostly headache, injection site pain, myalgia, fever, and fatigue. One serious adverse event of high-grade fever was classified possibly related to VLA1553. Among 81 adverse events of special interest (ie, symptoms suggesting chikungunya-like disease), 16 were classified as related to trial vaccination (15 in the VLA1553 group and one in the placebo group), mostly early onset events usually starting during the first week after vaccination. Late onset adverse events of special interest showed no medically relevant differences between treatment groups. Nine adolescents had short-lived, usually mild recurring episodes of arthralgia (seven with VLA1553 and two with placebo) with a median duration of 1 day (cumulative range 1–7 days). One further participant with a history of chikungunya virus infection experienced recurring arthralgia followed by long-term polyarthralgia in several joints starting 148 days post-vaccination, classified unrelated to VLA1553. None of the recurring events of arthralgia was medically attended.

Interpretation

VLA1553 was generally safe and induced seroprotective titres up to 12 months in nearly all adolescents, with favourable safety data in those who were seropositive. The data support the use of VLA1553 for the prevention of disease caused by the chikungunya virus among adolescents and in endemic regions.

Funding

Coalition for Epidemic Preparedness Innovations and EU Horizon 2020.

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.

Source:

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00631-0/abstract?rss=yes

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