Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Remodeled glycoprotein for broad protection against ebolaviruses

Award Number: R43AI136229
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: 01/26/2018
PERIOD OF PERFORMANCE END DATE: 12/31/2020

Group Awards By:

View Award Description

Remodeled glycoprotein for broad protection against ebolaviruses - Project summary The 2014-2015 Ebola virus disease (EVD) outbreak in West Africa, caused by the Zaire Ebola virus (EBOV), resulted in over 28,000 cases and 11,000 deaths. This has been a sobering reminder of the growing threat of the filoviruses for global public health. Driven by the unprecedented dimension of this outbreak, most of the efforts to develop vaccines against the different species of ebolaviruses has been focused on EBOV. However, other ebolavirus species such as Sudan virus (SUDV) and Bundibugyo virus (BDBV) have also caused sizable outbreaks in the past 20 years and the species causing future EVD outbreaks cannot be predicted. The vaccines currently in development, including adenovirus-based vaccines and VSV-ZEBOV that was successfully tested in a Phase III clinical trial in Africa, are specific to EBOV and do not provide cross protection against SUDV or BDBV. A major obstacle for elicitation of broadly neutralizing responses is the fact that most conserved regions of the ebolavirus glycoprotein (GP), including the receptor binding site (RBS), are largely concealed on the viral surface. Using a special immunogen cocktail we have recently isolated several broadly neutralizing monoclonal antibodies (bNAbs), characterized their epitopes in collaboration with Integral Molecular, and for the first time, identified a cocktail of two antibodies that simultaneously protects against EBOV, SUDV, and BDBV. This body of knowledge can now be exploited to develop a single vaccine that protects against all ebolaviruses. Our proposal is based on two key and novel observations. i) We have identified several residues in the base of the EBOV GP trimer that, when mutated, increase the exposure of broadly neutralizing epitopes on the apical face of GP, including the RBS that is otherwise largely concealed. We have also demonstrated that immunization with such mutants broadens the antibody response towards SUDV and BDBV. ii) We have demonstrated that a proteolytically remodeled form of GP representing the post-entry form of GP in the host endosomes binds to the most potent bNAbs with very high affinity, suggesting that this “cleaved GP” (GPCL) can be a candidate pan- ebolavirus vaccine. Building upon these observations, this Phase I project is designed in three specific Aims. In Aim 1, using the information gained from our extensive alanine scanning mutagenesis studies, a variety of mutants will be generated on the backbone of VSV-EBOV GP pseudotype virus, and their ability to elicit broadly neutralizing responses will be evaluated. Aim 2 focuses on generation and functional testing of immunogens based on GPCL. Additional specific mutations identified in Aim 1 will be incorporated into GPCL immunogen and evaluated in immunogenicity studies. In Aim 3, the best candidates identified in Aims 1 and 2 will be tested in proof of concept efficacy studies in murine challenge models of EBOV and SUDV. Upon successful proof of concept, we anticipate a phase II to demonstrate efficacy of the vaccine against EBOV, SUDV, and BDBV in non-humane primate models of infection as well as initiation of IND enabling studies.


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: 2022 ( Subtotal = -$116 )
2022	2019	INTEGRATED BIOTHERAPEUTICS INC	4 RESEARCH CT	POTOMAC	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	2	10/14/2021	NON-COMPETING CONTINUATION	-$116
														Subtotal = -$116

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	INTEGRATED BIOTHERAPEUTICS, INC.	4 RESEARCH COURT, SUITE 300	ROCKVILLE	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	003	2	9/2/2021	NON-COMPETING CONTINUATION	$299,186
2021	2019	INTEGRATED BIOTHERAPEUTICS, INC.	4 RESEARCH COURT, SUITE 300	ROCKVILLE	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	001	2	9/2/2021	NON-COMPETING CONTINUATION	-$299,186
2021	2018	INTEGRATED BIOTHERAPEUTICS, INC.	4 RESEARCH COURT, SUITE 300	ROCKVILLE	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	002	1	9/2/2021	NEW	$302,469
2021	2018	INTEGRATED BIOTHERAPEUTICS, INC.	4 RESEARCH COURT, SUITE 300	ROCKVILLE	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	1	9/2/2021	NEW	-$302,469
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $299,186 )
2019	2019	INTEGRATED BIOTHERAPEUTICS, INC.	4 RESEARCH COURT, SUITE 300	ROCKVILLE	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	2	12/26/2018	NON-COMPETING CONTINUATION	$299,186
														Subtotal = $299,186

Issue Date FY: 2018 ( Subtotal = $302,469 )
2018	2018	INTEGRATED BIOTHERAPEUTICS, INC.	4 RESEARCH COURT, SUITE 300	ROCKVILLE	MD	20850	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	1	1/26/2018	NEW	$302,469
														Subtotal = $302,469

Grand Total All Awards = $601,539

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Remodeled glycoprotein for broad protection against ebolaviruses

Award Number: R43AI136229

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: 01/26/2018

PERIOD OF PERFORMANCE END DATE: 12/31/2020

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer