Friday, August 15, 2025 8/15/2025

Self-Assembling Spike-EBR Nanoparticles as a Vaccine Platform Technology Against SARS-CoV-2 and Future Pandemic Coronaviruses

Award Number: DP5OD033362
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/22/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Self-Assembling Spike-EBR Nanoparticles as a Vaccine Platform Technology Against SARS-CoV-2 and Future Pandemic Coronaviruses - Project Summary/Abstract The COVID-19 pandemic represents the 3rd outbreak caused by zoonotic transmission of a beta-coronavirus (beta-CoV) in the last 20 years. Hence there is an urgent need for new vaccine strategies to control the ongoing pandemic and prevent future CoV outbreaks. mRNA vaccines have emerged as an ideal platform for the development of rapid-response vaccines, but clinical studies have shown that neutralizing antibody titers elicited by mRNA vaccines are ~10-fold lower than titers elicited by protein nanoparticle (NP) vaccines. This is a concern with regards to the emergence of SARS-CoV-2 variants of concern (VOCs) that are less sensitive to vaccine- induced antibodies. In addition, less than 25% of the world population is fully vaccinated. Thus, rapid-response vaccine technologies are needed that elicit potent antibody responses with a single injection and/or lower doses, to ensure lasting protection against VOCs, reduce costs, and accelerate global distribution. Moreover, prevention of future CoV pandemics requires the development of a universal CoV vaccine that elicits cross-reactive immune responses against a broad spectrum of CoV strains by focusing responses to conserved epitopes. The scope of the proposed research is to design and evaluate new vaccine strategies to enhance the potency of mRNA-based rapid-response vaccines and facilitate universal CoV vaccine development. The proposal is based on the EBR NP technology, which modifies membrane proteins such as CoV spike (S) proteins to self-assemble into virus- resembling NPs that bud from the cell surface. NP assembly is induced by inserting a short amino acid sequence into the cytoplasmic tail designed to recruit proteins from the endosomal sorting complex required for transport (ESCRT) pathway. Initial studies in mice showed that low-dose injections of EBR NPs presenting the SARS- CoV-2 S protein elicited 10-fold higher neutralizing antibody titers than soluble S protein and protein-based NPs that displayed the receptor-binding domain (RBD) of the S protein. The EBR NP technology will be applied to accomplish three goals: i) Design a hybrid mRNA vaccine encoding the modified SARS-CoV-2 S-EBR construct that would be expressed at the cell surface and self-assemble into virus-resembling NPs to elicit more potent antibody responses than the approved Pfizer/Moderna vaccines, while retaining the manufacturing properties and T-cell activation of mRNA vaccines. ii) Engineer S-EBR NPs to package and deliver S or S-EBR mRNA vaccines as an alternative to lipid NPs. This delivery approach would enhance mRNA vaccine potency as S proteins presented on S-EBR NPs induce potent antibody responses, facilitate efficient intracellular delivery, and target mRNA vaccines to tissues that are naturally infected by SARS-CoV-2 to induce local immune responses. iii) Design and evaluate mosaic S-EBR NP-based universal CoV vaccine candidates that present full-length membrane-associated S proteins from multiple CoV strains to elicit cross-reactive immune responses against a broad spectrum of CoVs and protect against future outbreaks. The proposed vaccine strategies could have direct impact on the COVID-19 global health crisis and advance our emergency preparedness for the next pandemic.


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 = $945,000 )
2025	2025	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Trans-NIH Research Support	005	4	8/8/2025	EXTENSION WITH OR WITHOUT FUNDS	$945,000
2025	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Trans-NIH Research Support	004	3	8/8/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Trans-NIH Research Support	002	3	10/25/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$466,931
2025	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Trans-NIH Research Support	003	3	4/16/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	001	2	10/25/2024	NON-COMPETING CONTINUATION	-$421,000
2025	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	1	10/25/2024	NEW	-$45,931
														Subtotal = $945,000

Issue Date FY: 2024 ( Subtotal = $472,500 )
2024	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Trans-NIH Research Support	001	3	9/12/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$472,500
2024	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	2	9/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $472,500

Issue Date FY: 2023 ( Subtotal = $421,000 )
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	2	8/31/2023	NON-COMPETING CONTINUATION	$421,000
														Subtotal = $421,000

Issue Date FY: 2022 ( Subtotal = $421,000 )
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	1	9/15/2022	NEW	$421,000
														Subtotal = $421,000

Grand Total All Awards = $2,259,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Self-Assembling Spike-EBR Nanoparticles as a Vaccine Platform Technology Against SARS-CoV-2 and Future Pandemic Coronaviruses

Award Number: DP5OD033362

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/22/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer