TY - JOUR
T1 - Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults
T2 - A phase 1 dose-escalation trial
AU - Chang, Lee Jah
AU - Dowd, Kimberly A.
AU - Mendoza, Floreliz H.
AU - Saunders, Jamie G.
AU - Sitar, Sandra
AU - Plummer, Sarah H.
AU - Yamshchikov, Galina
AU - Sarwar, Uzma N.
AU - Hu, Zonghui
AU - Enama, Mary E.
AU - Bailer, Robert T.
AU - Koup, Richard A.
AU - Schwartz, Richard M.
AU - Akahata, Wataru
AU - Nabel, Gary J.
AU - Mascola, John R.
AU - Pierson, Theodore C.
AU - Graham, Barney S.
AU - Ledgerwood, Julie E.
N1 - Funding Information:
The study was fully funded by the NIH intramural research programme. The vaccine was manufactured by the VRC (an intramural centre within the NIAID, NIH), and the VRC funded and undertook the study. The VRC 311 Study Team was responsible for the study design, study management, regulatory submissions to the NIAID Institutional Review Board and US FDA, data collection, data analysis, data interpretation, and writing of the report. The principal investigator and associate investigators had full access to all the data in the study and JEL had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/12/6
Y1 - 2014/12/6
N2 - Background Chikungunya virus - a mosquito-borne alphavirus - is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine.Methods 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 μg, 20 μg, or 40 μg on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358.Findings 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 μg (n=5), 20 μg (n=10), and 40 μg (n=10). The protocol was completed by all five participants at the 10 μg dose, all ten participants at the 20 μg dose, and eight of ten participants at the 40 μg 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 μg group, 1775 in the 20 μg group, and 7246 in the 40 μg group), and a significant boost occurred after the third vaccination in all dose groups (10 μg group p=0·0197, 20 μg group p<0·0001, and 40 μg 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 μg group, 4525 for the 20 μg group, and 5390 for the 40 μg group.Funding Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.Interpretation The chikungunya VLP vaccine was immunogenic, safe, and 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 and in more diverse populations.
AB - Background Chikungunya virus - a mosquito-borne alphavirus - is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine.Methods 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 μg, 20 μg, or 40 μg on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358.Findings 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 μg (n=5), 20 μg (n=10), and 40 μg (n=10). The protocol was completed by all five participants at the 10 μg dose, all ten participants at the 20 μg dose, and eight of ten participants at the 40 μg 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 μg group, 1775 in the 20 μg group, and 7246 in the 40 μg group), and a significant boost occurred after the third vaccination in all dose groups (10 μg group p=0·0197, 20 μg group p<0·0001, and 40 μg 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 μg group, 4525 for the 20 μg group, and 5390 for the 40 μg group.Funding Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.Interpretation The chikungunya VLP vaccine was immunogenic, safe, and 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 and in more diverse populations.
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U2 - 10.1016/S0140-6736(14)61185-5
DO - 10.1016/S0140-6736(14)61185-5
M3 - Article
C2 - 25132507
AN - SCOPUS:84919842605
SN - 0140-6736
VL - 384
SP - 2046
EP - 2052
JO - The Lancet
JF - The Lancet
IS - 9959
ER -
