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Structural mapping of an immunodominant antigenic site on the norovirus capsid

Award Number: R21AI180523
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/10/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Structural mapping of an immunodominant antigenic site on the norovirus capsid - PROJECT SUMMARY Noroviruses are a top cause of acute gastroenteritis globally, and no approved norovirus vaccine exists. The norovirus capsid protein plays key roles in virus attachment and entry into host cells and is the target of neutralizing antibodies. Recent genomics and serological studies predict the presence of a new antigenic site, named antigenic site G, and suggest that it became immunodominant during the emergence of the most recent GII.4 norovirus variant outbreak, revealing a novel mechanism for virus evolution immune escape. However, the molecular interactions of neutralizing antibodies targeting this immunodominant site on the norovirus capsid have not been described. Our goal is to define the epitopes that are recognized by neutralizing monoclonal antibodies targeting the immunodominant antigenic site G on the norovirus capsid and to directly visualize and map antibody immunodominance in serum antibodies targeting past and current norovirus variants. Using an integrated structural and biophysical approach, we will pursue two specific aims to (1) Define the epitopes of neutralizing monoclonal antibodies targeting the norovirus capsid antigenic site G and (2) Directly visualize the chronological shift in antibody immunodominance towards antigenic site G. Results obtained by this work will provide a molecular roadmap for the development of novel norovirus vaccine immunogens that broadly protect against norovirus infection and disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $234,750 )
2025	2025	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	2	5/23/2025	NON-COMPETING CONTINUATION	$234,750
														Subtotal = $234,750

Issue Date FY: 2024 ( Subtotal = $195,000 )
2024	2024	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	1	7/10/2024	NEW	$175,500
2024	2024	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$19,500
														Subtotal = $195,000

Grand Total All Awards = $429,750

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Structural mapping of an immunodominant antigenic site on the norovirus capsid

Award Number: R21AI180523

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/10/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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