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.

Keywords: immunogenicity; norovirus; safety; tolerability; vaccine.

Figure 1.

Study flow chart.

Figure 2.

Geometric mean titers (GMTs) (with 95% confidence intervals) of pan-immunoglobulin (A and B), immunoglobulin A (IgA; C and D), and histo-blood group antigen (HBGA)–blocking (E and F) antibodies against norovirus GI.1 and GII.4 virus-like particles at each of the sampling time points.