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Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial - 24/09/20

Doi : 10.1016/S1473-3099(20)30238-3 
Nina Wressnigg, PhD a, , Romana Hochreiter, PhD a, Oliver Zoihsl, MSc a, Andrea Fritzer, PhD a, Nicole Bézay, PhD a, Anton Klingler, PhD b, Karen Lingnau, PhD a, Martina Schneider, PhD a, Urban Lundberg, PhD a, Andreas Meinke, PhD a, Julian Larcher-Senn, PhD b, Irena Čorbic-Ramljak, PhD a, Susanne Eder-Lingelbach, MSc a, Katrin Dubischar, MSc a, Wolfgang Bender, MD a
a Valneva, Vienna, Austria 
b Assign Data Management and Biostatistics, Innsbruck, Austria 

* Correspondence to: Dr Nina Wressnigg, Valneva Austria, Vienna 1030, Austria Valneva Austria Vienna 1030 Austria

Summary

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 × 103 per 0·1 mL; medium dose 3·2 × 104 per 1 mL; or high dose 3·2 × 105 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.

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Vol 20 - N° 10

P. 1193-1203 - octobre 2020 Retour au numéro
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