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Updated: Dec 24, 2025
07:02
Quantifying Human Norovirus Virus-like Particles Binding to Commensal Bacteria Using Flow Cytometry
Published on: April 29, 2020
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Virus-Host Interactions Between Nonsecretors and Human Norovirus
Lisa C Lindesmith1, Paul D Brewer-Jensen1, Michael L Mallory1
1Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina.
Cellular and Molecular Gastroenterology and Hepatology
|April 15, 2020
Summary
Human norovirus infection immunity was studied in nonsecretors, revealing broad antibody and T-cell responses after GII.2 infection. This finding supports developing vaccines for GII.4 norovirus, especially for individuals with limited immunity.
Area of Science:
- Immunology
- Virology
- Gastroenterology
Background:
- Human norovirus is a leading cause of acute gastroenteritis.
- The FUT2 gene (secretor enzyme) determines susceptibility to norovirus strains.
- Nonsecretors (FUT2-/-) exhibit resistance to dominant GII.4 strains due to limited fucosylated histoblood group antigen carbohydrates (HBGA) expression.
Purpose of the Study:
- To evaluate the breadth of serologic and cellular immunity following natural GII.2 norovirus infection in nonsecretors.
- To investigate immune responses in a nonsecretor cohort, mimicking young children's limited immunity to GII.4 norovirus vaccines.
- To establish a model for studying cross-protection in the context of limited pre-exposure.
Main Methods:
- Utilized specimens from the first characterized nonsecretor cohort naturally infected with GII.2 human norovirus.
- Assessed serologic immunity using surrogate neutralization assays.
- Analyzed cellular activation and cytokine production via flow cytometry.
Main Results:
- GII.2 infection induced broad antibody and cellular immunity, persisting for at least 30 days (T cells, monocytes, dendritic cells) and 180 days (blocking antibody).
- Interferon-γ and tumor necrosis factor-α producing cellular lineages dominated the immune response.
- T-cell and B-cell responses demonstrated cross-reactivity with other GII strains but not GI strains; bile acids were essential for GII.2 binding to nonsecretor HBGAs.
Conclusions:
- Data support the development of within-genogroup, cross-reactive antibody and T-cell immunity.
- These immune responses may form the basis for eliciting broad immunity after GII.4 norovirus vaccination.
- Nonsecretors serve as a valuable model for studying GII.4 vaccine responses in individuals with limited immunity, including young children.
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