학술논문
A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adults.
Document Type
Article
Author
Source
Subject
*CHIKUNGUNYA virus
*IMMUNE response
*VIRAL vaccines
*ADULTS
*NEUTRALIZATION tests
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Language
ISSN
1195-1982
Abstract
Background The global spread of the chikungunya virus (CHIKV) increases the exposure risk for individuals travelling to or living in endemic areas. This Phase 3 study was designed to demonstrate manufacturing consistency between three lots of the single shot live-attenuated CHIKV vaccine VLA1553, and to confirm the promising immunogenicity and safety data obtained in previous trials. Methods This randomized, double-blinded, lot-to-lot consistency, Phase 3 study, assessed immunogenicity and safety of VLA1553 in 408 healthy adults (18–45 years) in 12 sites across the USA. The primary endpoint was a comparison of the geometric mean titre (GMT) ratios of CHIKV-specific neutralizing antibodies between three VLA1553 lots at 28 days post-vaccination. Secondary endpoints included immunogenicity and safety over 6 months post-vaccination. Results GMTs were comparable between the lots meeting the acceptance criteria for equivalence. The average GMT (measured by 50% CHIKV micro plaque neutralization test; μPRNT50) peaked with 2643 at 28 days post-vaccination and decreased to 709 at 6 months post-vaccination. An excellent seroresponse rate (defined as μPRNT50 titre ≥ 150 considered protective) was achieved in 97.8% of participants at 28 days post-vaccination and still persisted in 96% at 6 months after vaccination. Upon VLA1553 immunization, 72.5% of participants experienced adverse events (AEs), without significant differences between lots (related solicited systemic AE: 53.9% of participants; related solicited local AE: 19.4%). Overall, AEs were mostly mild or moderate and resolved without sequela, usually within 3 days. With 3.9% of participants experiencing severe AEs, 2.7% were classified as related, whereas none of the six reported serious adverse events was related to the administration of VLA1553. Conclusions All three lots of VLA1553 recapitulated the safety and immunogenicity profiles of a preceding Phase 3 study, fulfilling pre-defined consistency requirements. These results highlight the manufacturability of VLA1553, a promising vaccine for the prevention of CHIKV disease for those living in or travelling to endemic areas. [ABSTRACT FROM AUTHOR]