Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial

• Published in: The Journal of infectious diseases Vol. 214; no. 6; pp. 845 - 853
• Main Authors: Atmar, Robert L., Baehner, Frank, Cramer, Jakob P., Song, Eric, Borkowski, Astrid, Mendelman, Paul M.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.09.2016
• Subjects: Adjuvants, Immunologic - administration & dosage; Adolescent; Adult; Antibodies, Viral - blood; Caliciviridae Infections - prevention & control; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Healthy Volunteers; Humans; Immunoglobulin A - blood; Injections, Intramuscular; Major and Brief Reports; Male; Middle Aged; Norovirus; Norovirus - immunology; Placebos - administration & dosage; Time Factors; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - adverse effects; Vaccines, Virus-Like Particle - immunology; Virion; VIRUSES; Young Adult; vaccine; norovirus; safety; immunogenicity; tolerability
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiw259

Background. Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18–49 years. Methods. Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 μg or 50 μg of GI.1 VLP and 50 μg GII.4 VLP (15/50 and 50/50 formulations) adjuvanted with monophosphoryl lipid A and Al(OH)₃. We present safety and immunogenicity assessments up to 28 days after vaccination. Results. No vaccine-related serious adverse events or adverse events of special interest were reported. Reactions were mainly mild to moderate, the most frequent being transient pain, in 8%, 64%, and 73% of placebo, 15/50, and 50/50 groups, respectively; transient myalgia, headache, and fatigue were the commonest systemic adverse events. Subjects assessed per protocol (n = 442) displayed rapid immune responses to vaccination, peaking by days 7–10 and persisting through day 28. GI.1 responses were highest with the 50/50 formulation, but GII.4 responses were higher with the 15/50 formulation. Conclusions. Both candidate VLP vaccines were well tolerated and elicited robust immune responses by 7–10 days that persisted through day 28. The 15/50 formulation displayed the best balance of tolerability and immunogenicity.