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Protection and Immunity after Polyanhydride Nanoparticle Vaccination against Avian Influenza A Virus

Award Number: R01AI168001
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: 11/14/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Protection and Immunity after Polyanhydride Nanoparticle Vaccination against Avian Influenza A Virus - Influenza A virus (IAV) is a major cause of serious respiratory illness and has been responsible for significant morbidity and mortality in humans worldwide. Seasonal IAV infections lead to approximately 200,000 hospitalizations and 36,000 deaths annually in the United States during non-pandemic years. Furthermore, the IAV pandemics of 1918 (~50 million deaths worldwide), 1957-58 (~1 million deaths worldwide) and 1968-69 (~700,000 deaths worldwide) further demonstrate the impact of IAV on human health. The recent appearance of highly pathogenic H5N2 and the Eurasian highly pathogenic avian H5 viruses in the US as well as the high mortality rate observed in humans infected with the pre-pandemic avian H5N1 (~55-60% mortality rate) IAVs has heightened concerns. Thus, there has been a renewed interest in developing novel and efficacious influenza vaccination strategies that confer broad based protection to combat this significant global public health and pandemic threat. Recent studies have importantly shown that strategies that induce local (i.e. nasal mucosa and lung) tissue-resident memory T and B memory cells in addition to systemic immunity offer the greatest protection against future heterologous IAV encounters. The currently licensed IAV-vaccines by their design do not induce lung resident memory T and B cell responses. Thus, our long-term goal is to develop a protective universal vaccine against pre-pandemic avian IAV that induces lung and nasal resident T and B cells in addition to systemic immunity. We have developed a polyanhydride nanoparticle based IAV vaccine (IAV- nanovax) against seasonal IAV that breaks the cold chain, is needle free, and is biocompatible. This IAV- nanovax has shown efficacy in protection against homologous and heterologous seasonal IAV infections and the ability to induce T cell and B cell responses in the lungs and nasal passages. The HAs from H5 IAV are thought to be poorly immunogenic and require higher doses to be effective when compared to HAs from seasonal IAV thereby limiting vaccine design. Critically, our prior work with polyanhydride nanoparticles has also shown that they can induce robust immunity even at normally suboptimal levels of antigen. Therefore, this proposal will use the combined expertise of the PI and Co-Investigators and robust pre-clinical models to determine if a nanoparticle-based approach will allow for the induction of durable, IAV-specific, lung-resident T and B cell responses and broad-based protection against homologous and heterologous pre-pandemic avian IAV strains using the following Specific Aims: 1) Determine the efficacy of avian pre-pandemic IAV-nanovax in inducing robust local and systemic immunity and conferring protection against subsequent H5 IAV exposures, 2) Determine if apIAV-nanovax confers broad-based protection.


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 = $754,519 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	3	11/4/2024	NON-COMPETING CONTINUATION	$754,519
														Subtotal = $754,519

Issue Date FY: 2024 ( Subtotal = $755,681 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	001	2	5/13/2024	NON-COMPETING CONTINUATION	$75,567
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	2	10/30/2023	NON-COMPETING CONTINUATION	$680,114
														Subtotal = $755,681

Issue Date FY: 2023 ( Subtotal = $770,038 )
2023	2023	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	1	11/14/2022	NEW	$770,038
														Subtotal = $770,038

Grand Total All Awards = $2,280,238

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Protection and Immunity after Polyanhydride Nanoparticle Vaccination against Avian Influenza A Virus

Award Number: R01AI168001

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: 11/14/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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