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.
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.
