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Investigation into the activation of multiple bnAb precursors using structure-designed immunogens and Ig knock-in mice

Award Number: R01AI172627
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary HIV-1 vaccines that can elicit broadly neutralizing antibodies (bnAbs) are a primary goal. To date, it has been demonstrated that a single bnAb lineage (VRC01-class) can be specifically activated in human trials. Antibodies from this trial do not neutralize HIV-1 and heterologous sequential immunization is thought to be required to develop bnAbs. Heterologous sequential immunization has been employed to generate bnAbs in pre-clinical models. While VRC01-class antibodies isolated from infected individuals can be quite broad, the limit of breadth for VRC01-class antibodies induced by these types of vaccination strategies in people is unknown. Therefore, we are developing an alternative bnAb lineage targeting vaccine (VH1-46 class) through advanced protein engineering approaches and assessment in newly generated human immunoglobulin knock-in mice harboring VH1-46 germline antibodies. Further, we are pursuing innovative approaches to develop a dual bnAb lineage targeting vaccine which could synergize with current VRC01-class vaccines. Individual lineage targeting vaccines may not succeed at fully maturating these lineages, thus severely limiting the neutralization breadth and ultimate effectiveness of these vaccines. Dual lineage targeting may be critical for success of the first bnAb- eliciting HIV-1 vaccine.


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: 2024 ( Subtotal = $819,869 )
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	10/24/2023	NON-COMPETING CONTINUATION	$819,869
														Subtotal = $819,869

Issue Date FY: 2023 ( Subtotal = $843,126 )
2023	2023	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	11/3/2022	NEW	$843,126
														Subtotal = $843,126

Grand Total All Awards = $1,662,995

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Investigation into the activation of multiple bnAb precursors using structure-designed immunogens and Ig knock-in mice

Award Number: R01AI172627

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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