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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure.

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Human norovirus (GII.4) antibody responses change with age and exposure. Early infections target specific sites, while later immunity broadens, influencing future GII.4 variant potential.

Keywords:
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Area of Science:

  • Immunology
  • Virology
  • Public Health

Background:

  • Human norovirus GII.4 is a major cause of gastroenteritis, with evolving antigenic variants.
  • Adult antibody responses to GII.4 are influenced by immune memory, but pediatric responses are less understood.

Purpose of the Study:

  • To characterize the neutralizing antibody (nAb) landscape against GII.4 norovirus in relation to age and infection history.
  • To understand how antibody responses develop over a lifetime and influence susceptibility to new variants.

Main Methods:

  • Utilized a surrogate assay and antigenic site chimera virus-like particles to analyze GII.4 nAb responses.
  • Examined antibody reactivity against specific antigenic sites (A, C, G) and across different GII.4 variants.

Main Results:

  • The nAb landscape evolves with age and cumulative GII.4 exposure.
  • Initial infections elicit nAbs primarily targeting sites A and C; subsequent exposures broaden responses to include cross-site antibodies and site G.
  • Site G nAbs correlate with broader reactivity against diverse GII.4 variants, suggesting a role in enhanced protection.

Conclusions:

  • Immunity to GII.4 norovirus develops progressively throughout life, with distinct antibody profiles emerging after primary and subsequent infections.
  • The immunodominance of specific epitopes, like site G, can influence the breadth of protection and potentially impact the pandemic potential of future GII.4 variants.