Oral Norovirus Gastroenteritis Vaccine VXA-GI.1-NN Shows Efficacy
Sean N Tucker, PhD, highlighted that VXA-GI.1-NN demonstrated safety and efficacy in reducing norovirus infections, marking a potential treatment in prevention for a diverse range of demographics.
Norovirus (NV) is a leading cause of acute gastroenteritis globally, yet no specific therapy currently exists for norovirus gastroenteritis (NVG). VXA-GI.1-NN is a nonreplicating adenovirus-vectored thermostable oral vaccine that has demonstrated safety and tolerability in clinical trials, generating robust serum and mucosal immune responses. This study aimed to evaluate the safety, immunogenicity, and protective efficacy of VXA-GI.1-NN following challenge with NV GI.1. VXA-GI.1-NN was found to be safe and well tolerated among participants.
Sean N Tucker, PhD, CSO, VP of Research at Vaxart, presented this study at IDWeek 2024. e elaborates on the key findings regarding the vaccine's immunogenicity and efficacy compared to existing prevention methods. “We found a substantial decrease in the number of individuals infected with the norovirus vaccine tablet. From our standpoint, this was a wonderful result. Additionally, it was very important to note that because norovirus is easily transmitted, we observed that the amount of norovirus present in the vomit and feces of those challenged was significantly lower in the vaccine group compared to the placebo group. Given that norovirus is highly infectious, this finding could have broad implications.”
The vaccine induced strong serum and cellular immunogenicity, evidenced by substantial increases in VP1 GI.1-specific antibody-secreting cells (ASC) and serum antibodies. Serum functional antibody responses, as measured by the Norovirus Blocking Antibody Assay (NBAA), were significantly higher in the vaccine group compared to the placebo group. Additionally, VP1-specific IgA levels were significantly increased in nasal secretions and saliva of those who received the vaccine. The protective efficacy for preventing NVG was 21%, while the efficacy for preventing norovirus infection was 29%. Notably, there was an 85% reduction in geometric mean viral shedding in stool among participants who received VXA-GI.1-NN. A totality of evidence analysis across all six outcomes yielded a z-score of 5.56, indicating a protective benefit of the vaccine.
Tucker explains the demographic choice for the study, noting, “We used adults aged 18 to 49. They needed to be very healthy, as we were administering large amounts of the virus. It was crucial to ensure the population was relatively healthy. That said, we believe one of the main groups that would benefit from this vaccine is the elderly, who often have diminished immune responses. We previously conducted a study with the elderly that showed our vaccine elicited immune responses similar to those in younger individuals, suggesting the results could be reasonably applicable to an older population.”
In a randomized controlled trial, 165 healthy adults were split into two groups: one received a single oral dose of the VXA-GI.1-NN vaccine, and the other received a placebo. 28days after vaccination, 141 participants were exposed to a specific strain of norovirus. Researchers monitored for side effects for one week and tracked any adverse events for 28 days following exposure. They assessed the effectiveness of the vaccine by looking for cases of acute gastroenteritis caused by norovirus and measuring the amount of norovirus in stool and vomit samples using a specific test (qPCR). Immune responses were evaluated by measuring certain antibodies in blood and mucosal samples, and an overall analysis was conducted to determine the vaccine’s protective effect.
“As for the next steps, we are planning to conduct a phase 2b study and subsequently submit a package to the FDA to initiate phase 3 efficacy trials. One of the key advantages of our vaccine approach is that it comes in tablet form, differing from traditional injected vaccines, which are effective at generating serum responses. Our vaccine, delivered to the mucosal surface through swallowing, stimulates not only serum antibodies but also antibodies in the intestinal space. We believe these intestinal antibodies will be particularly important for combating norovirus, as it infects intestinal cells.”
In conclusion, VXA-GI.1-NN was demonstrated to be safe and immunogenic, effectively reducing both viral shedding and norovirus (NV) infection following challenge. The tableted VXA-GI.1-NN vaccine may help mitigate outbreaks by lowering viral shedding. The totality of evidence analysis indicated a strong statistical signal supporting the vaccine's protective effect, suggesting that it could play a vital role in public health strategies against norovirus outbreaks.
