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Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
Published on: June 24, 2012
An oral norovirus vaccine generates mucosal immunity and reduces viral shedding in a phase 2 placebo-controlled
Becca A Flitter1, Joshua Gillard2, Susan N Greco1
1Vaxart Inc., South San Francisco, CA 94080, USA.
Abstract:
There are currently no licensed vaccines for norovirus, a leading cause of epidemic and endemic gastroenteritis worldwide. Clinical advancement of promising vaccine candidates from phase 2 studies to phase 3 field trials has been hampered by the lack of robust immunological correlates of protection. Here, we conducted a phase 2b randomized, placebo-controlled vaccination and challenge study to assess the safety, efficacy, immunogenicity, and correlates of protection of VXA-G1.1-NN, an oral tablet norovirus vaccine. VXA-G1.1-NN was safe and well tolerated, conferred protection against norovirus GI.1 challenge, and reduced viral shedding in stool and emesis. Norovirus VP1-specific serum immunoglobulin A (IgA), IgG, and functional blocking antibody titers increased substantially after oral vaccination. Moreover, oral immunization stimulated VP1-specific IgA antibodies in nasal lining fluid, saliva, and fecal samples. Serum and mucosal antibody responses 7 days after vaccination were correlated with the induction of antibody-secreting, α4β7+ mucosal-homing B cells. Machine learning analyses of vaccine-stimulated immune components identified serum functional blocking antibody and fecal IgA as robust correlates of protection. These results demonstrate the potential of VXA-G1.1-NN as a safe and effective oral norovirus vaccine and reveal critical immunological features underpinning vaccine efficacy.
Insights
A new oral norovirus vaccine (VXA-G1.1-NN) shows promise, demonstrating safety and efficacy in a phase 2b study. It successfully protected against norovirus challenge and identified key immune responses as correlates of protection.
Area of Science:
- Vaccinology
- Gastroenterology
- Immunology
Background:
- Norovirus is a major cause of gastroenteritis globally, with no licensed vaccines currently available.
- Advancing norovirus vaccine candidates to clinical trials is hindered by the absence of reliable immunological correlates of protection.
Purpose of the Study:
- To evaluate the safety, efficacy, immunogenicity, and correlates of protection for VXA-G1.1-NN, an oral norovirus vaccine.
- To identify immunological markers that predict vaccine effectiveness against norovirus infection.
Main Methods:
- A phase 2b randomized, placebo-controlled study involving vaccination and subsequent norovirus challenge.
- Assessment of safety, tolerability, viral shedding, and various immune responses, including serum and mucosal antibodies.
- Machine learning analysis to identify robust correlates of protection from vaccine-stimulated immune components.
Main Results:
- VXA-G1.1-NN was found to be safe and well-tolerated.
- The oral vaccine provided protection against norovirus GI.1 challenge, reducing viral shedding.
- Oral vaccination significantly increased serum and mucosal antibodies (IgA, IgG) and induced mucosal-homing B cells.
- Functional blocking antibody titers in serum and fecal IgA were identified as strong correlates of protection.
Conclusions:
- VXA-G1.1-NN presents a potential safe and effective oral vaccine option for norovirus prevention.
- The study identified critical immunological correlates, including serum functional blocking antibodies and fecal IgA, which are essential for vaccine efficacy.
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