# Design and evaluation of a multivalent nanobody construct for prevention or treatment of SARS-CoV-2

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $397,382

## Abstract

Abstract
SARS-CoV-2 has spread rapidly across the globe. While vaccines are in development and
existing drugs have shown some efficacy in reducing disease severity, there is an urgent need
for molecules that can serve in both a prophylactic and therapeutic function. Proteins are well
suited for this task because they can be engineered to have high-specificity and high-affinity for
targets, and genetic protein fusion bestows multiple functions on a single protein molecule. A
nanobody (Nb) has been identified with high affinity for the receptor binding domain (RBD) of the
SARS-CoV-2 spike protein, which mediates viral entry into cells via the angiotensin converting
enzyme 2 (ACE2) receptor. Nbs are small heavy chain, single domain camelid antibodies that are
stable over wide conditions, express well in multiple systems, can be humanized to reduce
immunogenicity, and can be fused to other proteins. The goal of this proposal is to develop a
protein-based therapeutic platform that can be taken either prophylactically or post-infection to
reduce the severity of viral infection. The overall hypothesis is that a self-assembling hexameric
coiled-coli (Hex) can be fused to 12-24 anti-RBD Nbs to create a complex with high avidity that
will neutralize virus and prevent entry and/or aggregate virus into traps that can be cleared.
Further, anti-albumin Nb will be incorporated in the fusion design to investigate any benefit of
increased circulation time. Three aims have been set to meet the goal and test the hypothesis.
(1) Design, fabricate and characterize Hex-Nb assemblies made from fusion proteins with
different numbers of anti-RBD and anti-albumin Nbs. (2) Characterize binding, neutralization, and
trapping of SARS-CoV-2 pseudovirus by Hex-Nb fusion assemblies in vitro. (3) Determine
pharmacokinetics, biodistribution and humoral immunogenicity of Hex-nanobody fusion protein in
mice following intravenous injection. From this work, an innovative protein-based therapeutic will
be constructed from functional nanobodies that inhibits SARS-CoV-2 pseudovirus infection and
extends in vivo lifetime, providing proof of concept for Hex assemblies to serve as prophylactics
or therapeutics to prevent or treat viral infections. These results will enable future preclinical work,
including viral challenge studies and direct airway administration of the Hex-Nb assemblies.
Overall, this work will provide a strategy to respond to both the current and future pandemics with
highly multivalent engineered protein complexes.

## Key facts

- **NIH application ID:** 10235342
- **Project number:** 1R21EB031597-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Julie Champion
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,382
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235342

## Citation

> US National Institutes of Health, RePORTER application 10235342, Design and evaluation of a multivalent nanobody construct for prevention or treatment of SARS-CoV-2 (1R21EB031597-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10235342. Licensed CC0.

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