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Multiantigen-based universal influenza vaccine development with a versatile VLP platform

Award Number: R01AI192512
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2030

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Multiantigen-based universal influenza vaccine development with a versatile VLP platform - Project Summary/Abstract Current influenza vaccines induce strain-specific protection. Universal influenza vaccines are under active development to induce cross-protection against multiple influenza A viral strains. Conserved antigens (e.g., HA stems, M2e, NP, and M1) are attractive targets in universal influenza vaccine development. Although several universal influenza vaccines have been tested in clinical trials, results have been largely disappointing due to the induction of relatively weak immune responses. Highly immunogenic vaccine platforms are demanded to support universal influenza vaccine development. Recently we developed high-density flagellin-displayed hepatitis b core virus-like particles (FH VLPs) promising to support universal influenza vaccine development. FH VLPs activate innate immune systems and induce strong dendritic cell maturation. FH VLPs are superior to parent platforms to support M2e-based universal influenza vaccine and tumor vaccine development. Our recent studies found removal of D2 domain of flagellin and introducing SpyCatcher on FH VLP surface could further increase its immunogenicity and versatility to support vaccine development. This proposal will optimize HBc core and encapsulate CpG and identify optimal adjuvants to further boost vaccination. We hypothesize SpyCatcher-displayed and optimized FH VLPs provide a highly immunogenic platform for ‘plug-and-play’ vaccine development regardless of multimeric status and size of vaccine antigens. This proposal develops the optimized FH VLP-based M2e/HA stem and NP/M1 universal influenza vaccines and explores their separate and combined use to induce cross-protective immunity in the presence of optimal adjuvant(s) in preclinical animal models. Both group 1 and group 2 HA stems will be displayed together with M2e on the optimized FH VLP surface to induce potent cross-group protection. The optimized FH VLP platform will be also compared with mRNA to support universal influenza vaccine development. Longevity of protection, impact of pre-existing immunity, and vaccine efficacy in aged immune systems will be also evaluated in this proposal. Three specific aims are proposed with aim 1 about the optimization and preclinical development of FH VLP-based M2e/HA stem vaccine in murine models; aim 2 about the preclinical development of FH VLP-based NP/M1 vaccine in murine models; and aim 3 about the preclinical evaluation of FH VLP-based penta-antigen vaccine in murine and ferret models.


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 = $2,334,838 )
2026	2026	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE RD RM 103	KINGSTON	RI	02881	WASHINGTON	USA	Allergy and Infectious Diseases Research	000	1	8/20/2026	NEW	$2,334,838
														Subtotal = $2,334,838

Grand Total All Awards = $2,334,838

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Multiantigen-based universal influenza vaccine development with a versatile VLP platform

Award Number: R01AI192512

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2030

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