Tuesday, August 19, 2025 8/19/2025

Biophysical constraints of influenza neuraminidase evolution

Award Number: R01AI165475
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: 06/28/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Biophysical constraints of influenza neuraminidase evolution - PROJECT SUMMARY Seasonal influenza epidemic causes 3-5 million infections and 250,000 to 500,000 deaths every year. While seasonal influenza vaccine is available and being constantly updated, its effectiveness is often hampered by the rapid antigenic drift of circulating strains. As a result, a major goal of influenza research is to develop a more effective vaccine. Nevertheless, the poor ability to forecast the evolution of influenza virus poses a huge challenge in influenza vaccine development. Consequently, understanding how the evolutionary trajectories of influenza virus are being shaped can significantly benefit public health. Influenza virus has two surface antigens, namely hemagglutinin (HA) and neuraminidase (NA). While influenza vaccine development has traditionally focused on targeting the HA, NA has received increasing attention as an effective vaccine target in recent years. Evolution of NA is under several biophysical constraints including protein stability, surface expression, and enzymatic activity. These biophysical constraints determine not only the fitness effects of individual mutations, but also how these fitness effects vary in the presence of other mutations (i.e. epistasis). In fact, epistasis has been a main obstacle in evolution forecast since epistasis can lead to opposite fitness effects of the same mutation in different influenza strains. This proposed study will use innovative high- throughput experiments to systematically probe the fitness effects of all possible amino-acid mutations on NA and map epistatic interactions that are involved in the natural evolution of NA. In addition, the molecular mechanisms of epistasis will be characterized by biochemical and structural biology approaches. Statistical modeling will further be applied to quantify the relationships between biophysical constraints of NA and viral fitness. The results will comprehensively reveal the biophysical principles that govern the mutational fitness effects and epistatic interactions in influenza NA, and hence its evolutionary trajectories in natural evolution. This proposed study will therefore promote the construction of a unifying biophysical model to accurately forecast the evolution of influenza virus, which will in turn facilitate the development of next-generation influenza vaccines.


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 = $1,024,548 )
2025	2025	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	001	3	8/12/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,024,548
2025	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	2	8/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,024,548

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	2	6/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $512,274 )
2023	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	2	7/12/2023	NON-COMPETING CONTINUATION	$512,274
														Subtotal = $512,274

Issue Date FY: 2022 ( Subtotal = $512,274 )
2022	2022	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Allergy and Infectious Diseases Research	000	1	6/28/2022	NEW	$512,274
														Subtotal = $512,274

Grand Total All Awards = $2,049,096

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Biophysical constraints of influenza neuraminidase evolution

Award Number: R01AI165475

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: 06/28/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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