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Development and testing of RSV vaccines using a computational framework of virus-host interaction

Award Number: K01AI168445
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/21/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Development and testing of RSV vaccines using a computational framework of virus-host interaction - Respiratory Syncytial Virus (RSV) is the second leading cause of hospitalization in children worldwide and has been increasing appreciated as a cause of hospitalization and death in the elderly. Recent studies have shown that polyvalent vaccine formulations, mixture of antigens derived from distinct pathogen variants, can induce antibodies to regions conserved between those variants We hypothesize that polyvalent antigen RSV vaccine formulations will increase antibody to regions conserved between the antigens. By drawing on the natural variability that exists among RSV variants, we aim to study the effect that polyvalent RSV G or F antigen formulations have on the immune response. We will test if antibodies are enhanced towards regions conserved between the viral proteins with the polyvalent formulation. Aim 1. Determining the Effect of Polyvalent RSV Vaccine Formulations on Humoral Immunity using Computer Simulations. We hypothesize that RSV polyvalent vaccine formulations consisting of different combinations of G or F-protein antigens will increase the antibody response to conserved regions between the antigens. We will evaluate different vaccine formulations using a computational framework of virus/host- interaction (ssMod.v2). We will test for differences in antibody specificity between polyvalent and monovalent formulations in the framework. Antibody cross-reactivity and protection against RSV challenge will also be evaluated. Aim 2. Comparison of the Host Immune Response to Polyvalent Vaccine Formulations in Mice. We hypothesize that murine immunization with a mRNA-LNP vaccine comprising polyvalent antigen formulations will induce antibodies and immune cells specific to regions conserved between the antigens. mRNA-LNPs will be constructed using cap-1, codon-optimized, structure-stabilized mRNA, encoding G or F from A2 or B1 RSV variants and will be encapsulated using ionizable cationic lipids. Groups of mice will be immunized with either Aim 3. Test if RSV Polyvalent Vaccine Formulation Improves Protection from RSV Disease. We hypothesize that vaccine formulations containing polyvalent mixtures of G or F antigens will increase the extent of protection against RSV disease compared to monovalent formulations. Using different mixtures of mRNA- LNP, we will test the ability of polyvalent vaccines to protect against disease severity using a murine model of RSV challenge. The neutralizing antibody titer of the sera will be tested using a primary human lung epithelial cell RSV-neutralization assay. Monovalent and polyvalent vaccine formulations will be compared by testing for differences between infection and disease severity outcomes.


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: 2026 ( Subtotal = $101,672 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Allergy and Infectious Diseases Research	000	5	1/27/2026	NON-COMPETING CONTINUATION	$101,672
														Subtotal = $101,672

Issue Date FY: 2025 ( Subtotal = $101,672 )
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Allergy and Infectious Diseases Research	000	4	12/20/2024	NON-COMPETING CONTINUATION	$101,672
														Subtotal = $101,672

Issue Date FY: 2024 ( Subtotal = $101,672 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Allergy and Infectious Diseases Research	000	3	12/29/2023	NON-COMPETING CONTINUATION	$101,672
														Subtotal = $101,672

Issue Date FY: 2023 ( Subtotal = $101,672 )
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Allergy and Infectious Diseases Research	000	2	12/23/2022	NON-COMPETING CONTINUATION	$101,672
														Subtotal = $101,672

Issue Date FY: 2022 ( Subtotal = $101,672 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Allergy and Infectious Diseases Research	000	1	1/12/2022	NEW	$101,672
														Subtotal = $101,672

Grand Total All Awards = $508,360

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Development and testing of RSV vaccines using a computational framework of virus-host interaction

Award Number: K01AI168445

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/21/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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