A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults.

Publication Type
Journal Article
Year of Publication
Treanor, John J; Atmar, Robert L; Frey, Sharon E; Gormley, Robert; Chen, Wilbur H; Ferreira, Jennifer; Goodwin, Robert; Borkowski, Astrid; Clemens, Ralf; Mendelman, Paul M
J Infect Dis
Date Published
2014 Dec 01
Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Neutralizing; Antibodies, Viral; Caliciviridae Infections; Female; Follow-Up Studies; gastroenteritis; Humans; Injections, Intramuscular; Male; Middle Aged; norovirus; Vaccines, Virus-Like Particle; Viral Vaccines; Young Adult

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 µg, 15 µg, 50 µg, or 150 µg 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 µg 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 µg 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. Clinical Trials Registration. NCT01168401.