Oral Norovirus Vaccine Results

The data, which show strong and durable antibody responses and induction of norovirus-specific antibody and T cell responses, support immunogenicity of the vaccine candidate in a patient population that often has age-related reductions in immune responses to injected vaccines. Norovirus is a highly contagious virus that causes acute gastroenteritis (AGE) and can lead to substantial morbidity in older adults.

“A key finding of this study evaluating our first-generation oral pill norovirus vaccine candidate in elderly individuals was that the antibody and serum responses observed in these participants were robust and durable, and a cross-study analysis suggested that the observed antibody and cellular responses were independent of age. These findings are encouraging given that older adults have an increased risk of norovirus-related morbidity and may have less robust immune responses following vaccination compared with younger individuals,” said James F. Cummings, MD, Chief Medical Officer at Vaxart. “Another key result was that an orally-administered vaccine can generate potent antibody responses in mucosal tissues outside the gastrointestinal tract, which could have important implications for use of our vaccine platform for norovirus and other indications as well.”

The Phase Ib study evaluated the safety and immunogenicity of Vaxart’s oral norovirus vaccine candidate in two groups of healthy older adults aged 55-65 and 66-80 years old. The vaccine was administered orally at three dose levels by prime and boost, 28 days apart. Participants were randomized to receive vaccine or placebo at a 2:1 ratio, and 63 volunteers completed the study, which included safety and immunogenicity assessments through day 390.

Key findings from the study include: i) The vaccine candidate generated robust and durable serum antibody responses, with all three dose cohorts demonstrating statistically significant increases in serum anti-VP1 IgA compared to the placebo cohort on day 29 and day 57. No statistically significant differences were found between the two age groups within each dosing cohort. ii) Dose-dependent increases in vaccine-induced responses were also observed for serum anti-VP1 IgG in all vaccinated cohorts on day 29 and day 57 compared to pre-vaccination levels. iii) The vaccine induced VP1-specific IgA mucosal-homing antibody-secreting B cells and this response was independent of age. iv) The high-dose vaccine induced mucosal-homing T cells, which may contribute to protection against persistent infections. v) Oral administration of the vaccine stimulated strong and durable IgA responses in saliva and the nasal cavity. vi) Overall, the vaccine was safe and well tolerated in older adults. All solicited events were mild to moderate, with no grade 3 events related to the vaccine. Headache (14%) and malaise/fatigue (16%) were the most common solicited symptoms reported in the week following vaccine administration; headache (14%) and malaise/fatigue (14%) were reported at similar rates in the placebo group.

Vaxart previously reported that a Phase II challenge study of an oral pill norovirus vaccine candidate produced a statistically significant reduction in infection rate, a non-statistically significant reduction in norovirus AGE and a substantial reduction in viral shedding. A Phase I study in lactating mothers showed that the Company’s vaccine candidate resulted in a 4-6-fold increase in norovirus antibodies in breast milk, which may help to protect infants through passive antibody transfer. In January 2025, Vaxart announced that the next step in its norovirus program will be a Phase I, open label, dose ranging clinical trial evaluating its second-generation oral norovirus vaccine constructs head-to-head against its first-generation constructs. This trial is expected to initiate in the first half of 2025. 

Citation: An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase Ib clinical trial. Authors: Becca A. Flitter, Susan N. Greco, Colin A. Lester, Elena D. Neuhaus et al. Science Translational Medicine. 5 Mar 2025 Vol 17, Issue 788.