Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial.

Autor:	Wressnigg N; Valneva, Vienna, Austria. Electronic address: nina.wressnigg@valneva.com., Hochreiter R; Valneva, Vienna, Austria., Zoihsl O; Valneva, Vienna, Austria., Fritzer A; Valneva, Vienna, Austria., Bézay N; Valneva, Vienna, Austria., Klingler A; Assign Data Management and Biostatistics, Innsbruck, Austria., Lingnau K; Valneva, Vienna, Austria., Schneider M; Valneva, Vienna, Austria., Lundberg U; Valneva, Vienna, Austria., Meinke A; Valneva, Vienna, Austria., Larcher-Senn J; Assign Data Management and Biostatistics, Innsbruck, Austria., Čorbic-Ramljak I; Valneva, Vienna, Austria., Eder-Lingelbach S; Valneva, Vienna, Austria., Dubischar K; Valneva, Vienna, Austria., Bender W; Valneva, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	The Lancet. Infectious diseases [Lancet Infect Dis] 2020 Oct; Vol. 20 (10), pp. 1193-1203. Date of Electronic Publication: 2020 Jun 01.
DOI:	10.1016/S1473-3099(20)30238-3
Abstrakt:	Background: Chikungunya disease, which results in incapacitating arthralgia, has been reported worldwide. We developed a live-attenuated chikungunya virus (CHIKV) vaccine candidate designed for active immunisation of the general population living in endemic regions, as well as serving as a prophylactic measure for travellers to endemic areas. Methods: This single-blind, randomised, dose-escalation, phase 1 study investigated as primary outcome safety of a live-attenuated CHIKV vaccine candidate. At two professional clinical trial centres in Illinois and Alabama, USA, healthy volunteers aged 18-45 years were randomly assigned (1:1:2) to one of three escalating dose groups (low dose 3·2 × 10 3 per 0·1 mL; medium dose 3·2 × 10 4 per 1 mL; or high dose 3·2 × 10 5 50% tissue culture infection dose per 1 mL) and received a single-shot immunisation on day 0. Individuals in all groups were revaccinated with the highest dose on either month 6 or 12, and followed up for 28 days after revaccination. The safety analysis included all individuals who received the single vaccination; the immunogenicity analysis, which was a secondary outcome, included all individuals who completed the study without major protocol deviations (per-protocol population). The study is registered with ClinicalTrials.gov, NCT03382964, and is complete. Findings: The study was done between March 5, 2018, and Jul 23, 2019, with 120 adults recruited and enrolled between March 5 and June 21, 2018, and assigned to receive a low (n=31), medium (n=30), or high (n=59) dose of the vaccine. The vaccine was safe in the high-dose group and well tolerated in the low-dose and medium-dose groups. Four (7%) of 59 vaccinees in the high-dose group reported any local reaction, and 11 (36%), 12 (40%), and 40 (68%) volunteers in the low-dose, medium-dose, and high-dose groups, respectively, reported any solicited systemic reaction. No vaccine-related serious adverse events were reported. Data up to month 12 after a single immunisation of the 120 healthy volunteers showed a good immunogenicity profile with 100% seroconversion rates achieved at day 14 (103 [100%] of 103) and sustained for 1 year across all dose groups. Mean peak antibody titres at day 28 ranged from 592·6 to 686·9 geometric mean titres from the low-dose to high-dose groups, respectively. A single vaccination was sufficient to induce sustaining high-titre neutralising antibodies, as shown by the absence of an anamnestic response after any revaccination ranging from 94% to 100% of participants. Following revaccination, vaccinees were protected from vaccine-induced viraemia. Interpretation: A novel live-attenuated CHIKV vaccine was well tolerated and highly immunogenic in an adult population and could be an effective intervention for prophylaxis of chikungunya disease worldwide. Funding: Valneva, Vienna, Austria; Coalition for Epidemic Preparedness Innovation and EU Horizon 2020. (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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