# Defining clinically relevant viral epitopes with cow antibodies

> **NIH NIH R01** · APPLIED BIOMEDICAL SCIENCE INSTITUTE · 2021 · $352,893

## Abstract

Vaccines are the primary means by which to prevent, control, or eradicate infectious
diseases. While many vaccines have been successfully developed and have resulted in
enormous medical and veterinary benefit, there are certain viruses that have eluded
effective vaccine development. Generally, viruses with multiple strains or that have high
mutation rates can evade neutralizing antibodies, as their surface determinants are
variable and result in the inability of neutralizing antibodies raised against one strain to
bind and neutralize alternative strains. Certain rare epitopes, however, are required for
viral infection and are conserved across strains. Interestingly, neutralizing antibodies
against these rare epitopes tend to have long CDR H3 regions. In the case of HIV, long
CDR H3s can pierce the viral glycan shield and reach into the conserved epitope on the
gp120 spike protein. While long CDR H3 regions in human antibodies are infrequent in
the repertoire, cattle routinely produce long (20-40 amino acids) and ultralong (40-70
amino acids) CDR H3 regions that have unique “stalk” and “knob” structural features that
protrude far from the antibody surface. Therefore, cattle may be an excellent model
organism to identify and define new and conserved neutralizing epitopes in these
challenging viruses. Indeed, in preliminary experiments we have found that cattle make
a robust and broadly neutralizing antibody response to the HIV gp120 antigen. Here we
propose to use the unique cow antibody repertoire to define new conserved neutralizing
epitopes on two viruses of great importance to human and animal health, HIV and
BVDV. Effective vaccines against both of these viruses have been a major challenge to
develop. We will immunize animals against these viruses, generate monoclonal
antibodies that neutralize the virus as well as related strains, and molecularly map the
antigen-antibody interaction using mutagenesis and structural biology techniques.
Definition of new conserved epitopes could lead to engineered epitope-specific vaccines.
Thus, the outcomes of this proposal could enable generation of next-generation
vaccines for these two viruses, but could also have broad utility in vaccine development
against other challenging viruses in the future.

## Key facts

- **NIH application ID:** 10202672
- **Project number:** 5R01HD088400-05
- **Recipient organization:** APPLIED BIOMEDICAL SCIENCE INSTITUTE
- **Principal Investigator:** Vaughn Vasil Smider
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,893
- **Award type:** 5
- **Project period:** 2017-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202672

## Citation

> US National Institutes of Health, RePORTER application 10202672, Defining clinically relevant viral epitopes with cow antibodies (5R01HD088400-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10202672. Licensed CC0.

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