Autor(es): Chang Lee-Jah, Dowd Kimberly A, Mendoza Floreliz H, Saunders Jamie G, Sitar Sandra, Plummer Sarah H, Yamshchikov Galina, Sarwar Uzma N, Hu Zonghui, Enama Mary E, Bailer Robert T, Koup Richard A, Schwartz Richard M, Akahata Wataru, Nabel Gary J, Mascola John R, Pierson Theodore C, Graham Barney S, Ledgerwood Julie E

Resumo: Chikungunya virus--a mosquito-borne alphavirus--is endemic in Africa - south - southeast Asia - has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, - immunogenicity of a new c-idate vaccine. VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults aged 18-50 years who were enrolled at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Participants were assigned to sequential dose level groups to receive vaccinations at 10 ?g, 20 ?g, or 40 ?g on weeks 0, 4, - 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety - tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA - neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358. 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 ?g (n=5), 20 ?g (n=10), - 40 ?g (n=10). The protocol was completed by all five participants at the 10 ?g dose, all ten participants at the 20 ?g dose, - eight of ten participants at the 40 ?g dose; non-completions were for personal circumstances unrelated to adverse events. 73 vaccinations were administered. All injections were well tolerated, with no serious adverse events reported. Neutralising antibodies were detected in all dose groups after the second vaccination (geometric mean titres of the half maximum inhibitory concentration: 2688 in the 10 ?g group, 1775 in the 20 ?g group, - 7246 in the 40 ?g group), - a significant boost occurred after the third vaccination in all dose groups (10 ?g group p=0·0197, 20 ?g group p<0·0001, - 40 ?g group p<0·0001). 4 weeks after the third vaccination, the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 ?g group, 4525 for the 20 ?g group, - 5390 for the 40 ?g group. The chikungunya VLP vaccine was immunogenic, safe, - well tolerated. This study represents an important step in vaccine development to combat this rapidly emerging pathogen. Further studies should be done in a larger number of participants - in more diverse populations. Intramural Research Program of the Vaccine Research Center, National Institute of Allergy - Infectious Diseases, - National Institutes of Health.

Imprenta: Lancet, v. 384, n. 9959, p. 2046-2052, 2014

Identificador do objeto digital: 10.1016/S0140-6736(14)61185-5

Descritores: Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de publicação: 2014

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