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

ABSTRACT

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. CLINICAL TRIALS REGISTRATION NCT02142504.