Wednesday, June 18, 2025 6/18/2025

Structure, antigenicity, and function of HCMV fusogen gB

Award Number: R01AI164698
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: 06/08/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Structure, antigenicity, and function of HCMV fusogen gB - PROJECT SUMMARY/ABSTRACT Human cytomegalovirus (HCMV) is a highly successful human pathogens that infects much of the world’s population for life. While often asymptomatic, HCMV infections can cause severe disseminated disease in immunocompromised patients, e.g., transplant recipients, and developmental abnormalities in neonates. Hence, there is an urgent need for prophylactics to prevent viral transmission, especially from mother to fetus. HCMV glycoprotein B (gB) is both a key viral penetration protein and a dominant antigen for host defense. Unsurprisingly, gB is a component of all current HCMV vaccine candidates. However, vaccine efforts are stymied, at least in part, by an incomplete understanding of gB-specific immune responses. Moreover, the mechanistic contributions of gB to membrane fusion require further clarification. These gaps in our knowledge of both gB function and antigenicity largely stem from the reliance of research on the inactive, postfusion form of gB that cannot adequately recapitulate the active, prefusion form. We have successfully engineered soluble HCMV gB ectodomain in a prefusion form. Here, we propose to characterize its structure, antigenicity, and the mechanisms that control its activity. In Aim 1, we will determine the high-resolution structures of the prefusion HCMV gB and its complexes with known neutralizing antibodies. We will also stabilize prefusion gB for downstream applications (biochemical research and immunogen development). In Aim 2, we will isolate and characterize prefusion-gB-specific neutralizing antibodies from HCMV-seropositive donors. In Aim 3, we will investigate the regulatory mechanism that may restrain gB in its prefusion form. The proposal is innovative because, to our knowledge, this is the first time the soluble prefusion form of HCMV gB was successfully engineered. The proposal is significant because it will yield new mechanistic knowledge and provide new reagents that could aid in the development of optimal vaccines and passive immunization strategies against HCMV.


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 = $613,938 )
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	5/23/2025	NON-COMPETING CONTINUATION	$613,938
														Subtotal = $613,938

Issue Date FY: 2024 ( Subtotal = $613,938 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	6/14/2024	NON-COMPETING CONTINUATION	$613,938
														Subtotal = $613,938

Issue Date FY: 2023 ( Subtotal = $613,938 )
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	6/1/2023	NON-COMPETING CONTINUATION	$613,938
														Subtotal = $613,938

Issue Date FY: 2022 ( Subtotal = $758,575 )
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	6/21/2022	NON-COMPETING CONTINUATION	$758,575
														Subtotal = $758,575

Issue Date FY: 2021 ( Subtotal = $757,500 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	6/8/2021	NEW	$757,500
														Subtotal = $757,500

Grand Total All Awards = $3,357,889

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Structure, antigenicity, and function of HCMV fusogen gB

Award Number: R01AI164698

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: 06/08/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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