Safety, tolerability and immunogenicity of a quadrivalent recombinant norovirus vaccine (Pichia pastoris) in participants six weeks of age or older: Phase I/IIa trial.

Noroviruses are the leading cause of epidemic acute gastroenteritis and foodborne diarrheal disease in humans. Here, a randomized, double-blind, multi-cohort, placebo-controlled clinical trial was performed to determine the candidate vaccine's safety and immunogenicity. The experimental framework incorporated an initial Phase I age/dose-escalation stage followed by a Phase IIa dose-expansion component. A total of 580 participants (five groups: 6 weeks to 23 months, 2-5 years, 6-17 years, 18-59 years, and ≥60 years) were randomized into 13 groups to receive intramuscular injections of either a placebo (aluminium-containing or aluminium-free) or vaccine formulation (low-dose or high-dose) on days 0, 30 and 60. The safety outcomes included the incidence of all adverse events within 0-30 days post-vaccination and all serious adverse events within 6 months. Immunogenicity analyses focused on seroconversion rates against four norovirus genotypes (GI.1, GII.3, GII.4, GII.17) at 30 days post-third vaccination, including IgA, IgG and histoblood group antigen (HBGA)-blocking antibodies (BT50). The results of the Phase I and Phase IIa clinical trials indicated that the IgA seroconversion rates against the four norovirus genotypes at 30 days post-third vaccination were 49.45-86.81% in the low-dose group versus 66.12-85.25% in the high-dose group. IgG seroconversion ranged from 63.74% to 93.41% (low-dose) and 72.13% to 92.35% (high-dose), while HBGA-blocking antibody responses ranged from 64.84-86.26% (low-dose) and 78.14-89.62% (high-dose). Adverse reactions predominantly occurred within 0-7 days post-vaccination, with Grade 1-2 events predominating. The most frequent reactions included injection-site pain and fever. This trial is registered at www.chictr.org.cn (ChiCTR2400089762).