# Interdisciplinary protein engineering approach to design high affinity antibodies for flaviviruses

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $417,500

## Abstract

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.

## Key facts

- **NIH application ID:** 9823865
- **Project number:** 5R01AI141816-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Andras Fiser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,500
- **Award type:** 5
- **Project period:** 2018-11-15 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823865

## Citation

> US National Institutes of Health, RePORTER application 9823865, Interdisciplinary protein engineering approach to design high affinity antibodies for flaviviruses (5R01AI141816-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9823865. Licensed CC0.

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