A Novel Intramuscular Bivalent Norovirus Virus-Like Particle Vaccine Candidate-Reactogenicity, Safety, and Immunogenicity in a Phase 1 Trial in Healthy Adults
06/2014
Journal Article
Authors:
Treanor, J.J.;
Atmar, R.L.;
Frey, S.E.;
Gormley, R.;
Chen, W.H.;
Ferreira, J.;
Goodwin, R.;
Borkowski, A.;
Clemens, R.;
Mendelman, P.M.
Secondary:
J Infect Dis
Volume:
pii: jiu33
URL:
http://www.ncbi.nlm.nih.gov/pubmed/24951828
Keywords:
gastroenteritis; norovirus; vaccine; virus-like particle
Abstract:
BACKGROUND: Noroviruses are the most important viral causes of gastroenteritis-related morbidity and mortality. A randomized, double-blind, placebo-controlled study evaluated an adjuvanted bivalent intramuscular norovirus virus-like particle (VLP) vaccine. METHODS: Forty-eight adults aged 18-49 years received either 2 doses containing genotype GI.1 VLP and a consensus GII.4 VLP or 2 doses of placebo. Doses (5 microg, 15 microg, 50 microg, or 150 microg of each VLP) were administered 4 weeks apart in the first stage. Subsequently, 54 adults, aged 18-49 (n = 16), 50-64 (n = 19), and 65-85 (n = 19) years, received 2 doses of vaccine containing 50 microg of each VLP. Total and class-specific antibody responses, as well as histoblood group antigen (HBGA) blocking antibody responses, were measured before and after each dose. RESULTS: Local reactions were mainly injection site pain/tenderness, with no reported fever or vaccine-related serious adverse events. One dose of vaccine containing 50 microg of each VLP increased GI.1 geometric mean titers (GMTs) by 118-fold, 83-fold, and 24-fold and increased GII.4 GMTs by 49-fold, 25-fold, and 9-fold in subjects aged 18-49, 50-64, and 65-83 years, respectively. Serum antibody responses peaked at day 7 after the first dose, with no evidence of boosting following a second dose. Most subjects achieved HBGA-blocking antibody titers of >/=200. CONCLUSIONS: The vaccine was well tolerated and immunogenic. Rapid immune response to a single dose may be particularly useful in military personnel and travelers and in the control of outbreaks.
