# Structure-guided neutralizing antibodies developed using EpiVolve technology

> **NIH NIH R44** · ABBRATECH, INC. · 2023 · $296,100

## Abstract

Abstract
Current strategies for developing neutralizing Abs are not effective and typically involve screening IgGs from
recovered patients. Pandemic viruses evolve for mutations that can shield their epitopes from host immune
surveillance system, so a lot of important epitopes will be missed. Even after neutralizing Abs isolated are
from human sample, they still need further characterization using epitope binning and determination of
specificities to avoid off target effect. A systematic method for exploring the entire protein surface of a virus
that can identify all potential sites on the virus which can affect its life cycle would have significant impact and
is needed. We propose a structure-guided systematic Ab development pipeline to discover Abs that
can fight infectious diseases. We propose using our novel site-directed Ab development technology,
‘EpiVolve’ (short for Epitope Evolution). EpiVolve will be used to develop site-specific Abs to solvent-exposed
residues and the adjacent ‘context’ sequences. These Abs will be used for fighting infectious disease. The
advantages of EpiVolve are a) overcoming immune tolerance and targeting virus’ human proteome-mimicking
epitopes, b) precisely targeting any antigenic epitopes regardless of its immunogenicity, c) taking advantage
of B cell expansion and somatic hypermutation to generate IgG clonotypes against one targeted residue,
which allows an ability to generate both pan-variants Abs and polymorphism-specific Abs, and d) an ability
for generating a neutralizing Ab discovery pipeline. We will model this on SARS-cov-2 virus in Phase I and
Influenza A in Phase II. EpiVolve developed site-specific antibodies will target solvent-exposed residues on
the protein surface. Structure-guided Ag design will empower the EpiVolve technology in this systematic
analysis. For this proposal, we will present the current preliminary data on the pilot EpiVolve study on SARS-
cov-2 Receptor Binding Domain (RBD), focused mainly on the host cell receptor ACE2 binding interface. For
Phase I studies, we propose to complete the pilot study and extend the study to the whole protein surface of
the RBD domain. Characterizing each Ab by its binding affinity and ability to neutralize SARS-cov-2 virus will
be included in Phase I studies. For Phase II, we propose to apply the learnings from this Phase I study on
another virus model of great importance, the Influenza A virus. Specifically targeting the solvent-accessible
residues of the conserved Stem/Stalk region of the Hemagglutinin (HA) protein

## Key facts

- **NIH application ID:** 10698958
- **Project number:** 1R44AI177126-01
- **Recipient organization:** ABBRATECH, INC.
- **Principal Investigator:** Xiaofeng Li
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $296,100
- **Award type:** 1
- **Project period:** 2023-05-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698958

## Citation

> US National Institutes of Health, RePORTER application 10698958, Structure-guided neutralizing antibodies developed using EpiVolve technology (1R44AI177126-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10698958. Licensed CC0.

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