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Vaccine design to augment protective efficacy of antibodies against the EBV gH/gL glycoprotein complex

Award Number: R01AI147846
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: 08/09/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Vaccine design to augment protective efficacy of antibodies against the EBV gH/gL glycoprotein complex - PROJECT SUMMARY/ABSTRACT Relative to the general population, immunocompromised individuals, including those infected with HIV- have an elevated risk of developing Non-Hodgkin's Lymphomas, including plasmablastic lymphoma, primary central nervous system lymphoma, primary effusion lymphoma and diffuse large B-cell lymphoma. Many of these malignancies are driven by Epstein-Barr virus (EBV) and result from poor immune control of the virus driven by immune dysfunction. In addition, EBV can cause infectious mononucleosis (IM) which is major cause of morbidity in the adolescent population and a significant cause of lost time for new recruits in the US military. IM is also associated with an elevated lymphoma risk in the general population and a risk factor for developing multiple sclerosis. Thus, a safe and effective vaccine that prevents EBV infection and eliminates the EBV-driven morbidity would have a significant clinical benefit in the global population, and in HIV-1 infected individuals in particular. Previously, our lab identified that the virally encoded gH/gL glycoprotein complex is a critical target of antibodies that neutralize EBV infection. With our colleagues at HDT Bio, we recently developed a (Self-Amplifying Formulation-Enhanced Replicon) gH/gL vaccine that elicits antibodies that provide protection against experimental EBV infection in animal models. The goal of this proposal is to take advantage of the modularity of the SAFER platform to deliver additional viral antigens in a multivalent vaccine with a goal of eliciting potent neutralizing antibodies that are augmented by robust T cell responses that attack several stages of the viral life cycle. Importantly, we will use rational immunogen design to improve the safety of the vaccine antigens. We propose to evaluate the ability of multivalent vaccines developed here to protect against EBV challenge and/or tumor development in human immune system mice in prophylactic and therapeutic settings. Success here will support further development of EBV vaccines in humans.


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 = $857,804 )
2026	2026	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	7	3/30/2026	COMPETING CONTINUATION	$857,804
2026	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	6	1/27/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $857,804

Issue Date FY: 2023 ( Subtotal = $763,782 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	6	7/20/2023	NON-COMPETING CONTINUATION	$763,782
														Subtotal = $763,782

Issue Date FY: 2022 ( Subtotal = $763,782 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	5	7/21/2022	NON-COMPETING CONTINUATION	$763,782
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	004	4	9/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$21,517
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	003	3	9/27/2022	NON-COMPETING CONTINUATION	-$21,517
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	5/27/2022	NON-COMPETING CONTINUATION	-$392,604
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	4	5/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$392,604
														Subtotal = $763,782

Issue Date FY: 2021 ( Subtotal = $825,382 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	7/21/2021	NON-COMPETING CONTINUATION	$825,382
														Subtotal = $825,382

Issue Date FY: 2020 ( Subtotal = $825,382 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	2	6/22/2020	NON-COMPETING CONTINUATION	$825,382
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	2	9/17/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $825,382

Issue Date FY: 2019 ( Subtotal = $765,542 )
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	8/8/2019	NEW	$765,542
														Subtotal = $765,542

Grand Total All Awards = $4,801,674

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Vaccine design to augment protective efficacy of antibodies against the EBV gH/gL glycoprotein complex

Award Number: R01AI147846

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: 08/09/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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