Vaxart Oral Pill Bivalent Norovirus Vaccine Clinical Trials, Dosage, Indication, News, Side Effects
Vaxart Inc.'s GI.1/GII.4 oral pill bivalent norovirus vaccine candidate consisting of monovalent GII.4 VXA-G2.4-NS and GI.1 VXA-G1.1-NN is designed to prevent illness from norovirus, a very contagious virus that causes vomiting and diarrhea. Norovirus GI.1 Norwalk VP1 Vaccine (VXA-G1.1-NN), an Oral E1/E3-Deleted Replication-Defective Recombinant Adenovirus serotype 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant. The vaccine vector encodes for a full-length VP1 gene from the Norwalk virus (NV). The adjuvant is a short hairpin RNA (shRNA), expressed as a 21 nucleotide sequence (GAAACGA TATGGGCTGAATAC) as a tandem sequence in forward and reverse orientations separated by six nucleotides that comprise the loop of the RNA. The final drug product is formulated into an enteric-coated tablet. Vaxart's vaccine is differentiated from other norovirus candidates because it generates systemic and mucosal immunity delivered through the mouth and is stable at room temperature.
Vaxart reported topline data from the Phase 1 clinical trial, which focused on lactating mothers, on April 30, 2024. In the breast milk of lactating mothers who received the Vaxart vaccine candidate in the high-dose group, antibodies to norovirus rose on average fourfold for the G1.1 virus strain and sixfold for the GII. 4 virus strain. There were no vaccine-related serious adverse events and no dose-limiting pharmacotoxicity.
On March 6, 2025, Vaxart announced that data from the Phase 1b trial in elderly adults (55-80 years), which show strong and durable antibody responses and induction of norovirus-specific antibody and T cell responses, support the vaccine candidate's immunogenicity in a patient population that often has age-related reductions in immune responses to injected vaccines. On March 11, 2025, Vaxart announced initiating a Phase 1, open-label, dose-ranging clinical trial evaluating its second-generation oral norovirus vaccine constructs head-to-head against its first-generation constructs. Vaxart expects to conduct a Phase 2 safety and immunogenicity study that could begin as early as the second half of 2025, followed by an End of Phase 2 meeting with the U.S. Food and Drug Administration. A Phase 3 trial could then begin as early as 2026.
South San Francisco, CA-based Vaxart Inc. is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform. Vaxart believes a vaccine that produces mucosal antibodies locally in the intestine and systemic antibodies circulating in the blood may better protect against norovirus infection than an injectable vaccine.
Vaxart Oral Bivalent Norovirus Vaccine Indication
Norovirus is the leading cause of acute viral gastroenteritis in all age groups in the U.S. Approximately 3 million parents are forced by norovirus infections to miss work, on average, 2.2 days, to care for their children. The annual disease burden from norovirus is $10.6 billion in the U.S. alone. Globally, norovirus has become the leading cause of pediatric gastroenteritis in healthcare settings in countries adopting a rotavirus vaccine program.
Vaxart Oral Bivalent Norovirus Vaccine Dose
Dose: The vaccine was administered orally at three dose levels by prime and boost, 28 days apart.
Vaxart Oral Bivalent Norovirus Vaccine Adverse Events
The Phase 2 dose-ranging study also demonstrated that the bivalent norovirus vaccine candidate was well tolerated, with a favorable safety profile that included no vaccine-related serious adverse events and no dose-limiting toxicity. The Phase 1b study found 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 commonly 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 Oral Bivalent Norovirus Vaccine News
March 6, 2025 - "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 than 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."
April 30, 2024 - Dr. James F. Cummings, a Medical Officer, commented in a press release: "It can be difficult to immunize the youngest children mucosally because the immune system is still developing. Passive transfer of antibodies from mothers to infants via breast milk is potentially an innovative approach to improve infection resistance in infants."
December 21, 2023 - "This is an important step forward as we drive toward a vaccine candidate that may make it possible for mothers to protect their children against this highly contagious – and potentially lethal- virus. We look forward to announcing topline data from this study by the end of 2024," said Dr. James F. Cummings, Vaxart's Chief Medical Officer.
November 2, 2023: Dr. James F. Cummings, Vaxart's chief medical officer, comments, "We believe an oral norovirus vaccine pill may one day allow mothers to protect their infants against this highly contagious virus for which no approved vaccine is currently available."
September 6, 2023 - Challenge studies use higher quantities of virus than an individual may encounter during a naturally occurring infection. Yet, our vaccine candidate demonstrated a significant effect on infection and viral shedding, even though it did not achieve a statistically significant reduction in norovirus AGE," said Dr. James F. Cummings.
Vaxart Oral Bivalent Norovirus VXA-G1.1-NN Clinical Trials
Phase 1 multicenter, randomized, double-blind, placebo-controlled single dose, dose-ranging study is designed to evaluate the safety, tolerability, and immunogenicity of orally administered bivalent GI.1/GII.4 norovirus vaccine in healthy lactating females of at least 18 years of age and their breast-feeding infants (aged 30 days to 11 months). The study is expected to enroll approximately 76 subjects at seven sites in South Africa. Subjects will be randomized into high- or low-dose vaccine (N=30 for each arm) or placebo (N=16).
This is a phase 2b randomized, double-blind, placebo-controlled vaccination and challenge study to assess the protective efficacy of the Vaxart Norovirus vaccine (VXA-G1.1-NN). Healthy adults will be randomized in a 1:1 ratio to receive one oral dose of vaccine or placebo.
Clinical Trial NCT03897309: Safety & Immunogenicity Study of Ad5 Based Oral Norovirus Vaccines (VXA-NVV-103)
Clinical Trial NCT02868073: Phase 1 Placebo-controlled, Randomized Trial of an Adenoviral-vector Based Norovirus Vaccine (Completed)
Clinical Trial NCT03125473: Dose-Optimization Trial of VXA-G1.1-NN in Healthy Volunteers (Completed).
