A NEW orally administered norovirus vaccine tablet has demonstrated promising safety and immunogenicity in a clinical trial involving older adults, a group particularly vulnerable to severe outcomes from norovirus infection. The trial assessed the novel vaccine candidate VXA-G1.1-NN, which utilises a nonreplicating adenoviral vector to stimulate immune responses in the small intestine.
The randomised, double-blind, placebo-controlled study enrolled healthy participants aged 55–80 years, divided into two age groups. The vaccine was administered in three different dose levels via a prime and boost schedule, with doses given 28 days apart. The trial aimed to evaluate safety and immunogenicity by measuring antibody responses and mucosal immune markers over a 210-day period. Participants were monitored for adverse events, including local and systemic reactions, to determine tolerability.
VXA-G1.1-NN was well tolerated at all dose levels, with only mild-to-moderate solicited symptoms reported and no serious vaccine-related adverse events. The vaccine induced VP1-specific serum IgG and IgA antibodies in a dose-dependent manner, with levels significantly elevated at 28 days postvaccination and sustained for 210 days.
Functional antibodies were also detected, alongside a robust presence of circulating VP1-specific IgA antibody-secreting cells just one week postvaccination. Additionally, mucosal responses were observed, with VP1-specific IgA increasing in saliva and nasal lining fluid by Day 28 and persisting above baseline through Day 210. The presence of IgA+ plasmablasts expressing the mucosal-homing marker α4β7 further highlighted the vaccine’s ability to generate durable immune responses at mucosal sites.
These findings establish that oral administration of VXA-G1.1-NN is both safe and immunogenic in older adults up to 80 years of age. The durable systemic and mucosal responses observed suggest that this vaccine could offer a promising strategy for norovirus prevention in vulnerable populations.
Ada Enesco, EMJ
Reference
Flitter BA et al. An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial. Sci Transl Med. 2025;17(788):eads0556.
