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Interdisciplinary protein engineering approach to design high affinity antibodies for flaviviruses

Award Number: R01AI141816
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Recombinant monoclonal antibodies considered a new modality of therapeutic treatment to fight viral infections. A particular challenge for viral mAb development is the isolation and characterization of mAbs with broadly neutralizing activity (bNAbs) against multiple members of a single viral family to provide an immunotherapeutic advantage, particularly for infectious agents whose cases can progress rapidly toward serious disease. Our goal for the identification of bNAbs is protein engineering by a synergistic combination of computational and experimental methods, to enhance the breadth and potency of a specific mAb using designed mutations. Phage display provides an efficient way to randomly explore up to 1010 unique library members simultaneously. However, a typical antibody-antigen interface of ~15 residues present a combinatorial possibility of 2015 mutational variants, only a fraction of which can be sampled. As a result, phage display and other antibody combinatorial methods are reliant on restriction of either amino acid diversity or interfacial positions, which limits the effectiveness of the approach. To circumvent this limitation, we propose to develop an interdisciplinary approach where computationally designed, residue-based pharmacophore descriptions of the antibody-antigen interface are used to direct the library design in subsequent phage display experiments. As a test bed for this method, we will engineer novel bNAbs against flaviviruses, which include the globally important pathogens dengue virus and Zika virus.


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: 2023 ( Subtotal = $417,500 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	6	11/3/2022	NON-COMPETING CONTINUATION	$417,500
														Subtotal = $417,500

Issue Date FY: 2022 ( Subtotal = $417,500 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	5	10/13/2021	NON-COMPETING CONTINUATION	$417,500
														Subtotal = $417,500

Issue Date FY: 2021 ( Subtotal = $417,500 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	4	10/30/2020	NON-COMPETING CONTINUATION	$417,500
														Subtotal = $417,500

Issue Date FY: 2020 ( Subtotal = $417,500 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	3	11/8/2019	NON-COMPETING CONTINUATION	$417,500
														Subtotal = $417,500

Issue Date FY: 2019 ( Subtotal = $417,500 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	003	1	5/17/2019	NEW	-$36,373
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	002	2	2/8/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$345,444
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	001	1	2/8/2019	NEW	-$345,444
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	004	2	5/17/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$36,373
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	1	11/15/2018	NEW	$417,500
														Subtotal = $417,500

Grand Total All Awards = $2,087,500

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Interdisciplinary protein engineering approach to design high affinity antibodies for flaviviruses

Award Number: R01AI141816

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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