A Novel Intramuscular Bivalent Norovirus Virus-Like Particle Vaccine Candidate—Reactogenicity, Safety, and Immunogenicity in a Phase 1 Trial in Healthy Adults

• Published in: The Journal of infectious diseases Vol. 210; no. 11; pp. 1763 - 1771
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.12.2014
• Subjects: Adolescent; Adult; Age groups; Aged; Aged, 80 and over; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Blood groups; Caliciviridae Infections - prevention & control; Dosage; Female; Follow-Up Studies; Gastroenteritis - prevention & control; Humans; Immune response; Infections; Injections, Intramuscular; Major and Brief Reports; Male; Middle Aged; Norovirus; Norovirus - immunology; Placebos; Vaccination; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - adverse effects; Vaccines, Virus-Like Particle - immunology; Viral vaccines; Viral Vaccines - administration & dosage; Viral Vaccines - adverse effects; Viral Vaccines - immunology; VIRUSES; Young Adult; vaccine; gastroenteritis; norovirus; virus-like particle
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiu337

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.