# Mechanisms of Enhanced Neutralizing Antibody Responses to Rhinovirus C

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $792,076

## Abstract

PROJECT SUMMARY:
Rhinovirus (RV) is the predominant cause of the common cold, a major contributor to virus-induced
exacerbations of asthma, and infants who wheeze with RV infections are at increased risk for developing asthma.
Of the three RV species (A, B and C), RV-C is a major contributor to wheezing illnesses and exacerbations of
asthma in young children. In contrast to serologically characterized RV-A and B, current classification of RV-C
is based solely on sequence identity in the VP1 region and whether these genotypes correspond to unique
serotypes is unknown. Children with a single nucleotide polymorphism (SNP, rs6967330) in CDHR3 gene,
encoding the cellular receptor for RV-C, are at greatest risk for RV-C infections and illnesses. This coding SNP
is also a risk factor for early onset childhood asthma. There are no specific antivirals or vaccines for treatment
and prevention of RV-C induced illnesses but vaccination to prevent RV infections (and particularly RV-C in
young children with the CDHR3 SNP) could have major public health impact. Our recent studies in animal models
have demonstrated the feasibility of polyvalent inactivated RV vaccine antigens. New discoveries related to RV-
C structure, naturally-acquired immunity and human monoclonal antibody production will help us to fill existing
knowledge gaps and develop RV-C vaccine approaches suitable for clinical trials. Little is known about the
mechanisms of neutralizing antibody responses to RV-C. Neutralizing epitopes for RV-A and RV-B were mapped
to the most prominent surface protrusions of capsid proteins. Interestingly, the first cryo-EM atomic structure of
RV-C revealed unique, protruding “finger-like” spikes, formed by VP1, predicted to be dominant immunogenic
epitopes. We will test for type-specific and cross-reactive epitopes in these capsid structures. Another recent
discovery is that humoral immunity to RV-C (compared to other RVs) is more rapidly acquired with age. We
hypothesize that infections with RV-C can induce stronger, more cross-reactive neutralizing antibody responses
of longer duration compared to RV-A, due to (i) their ability to induce more severe illnesses in young children,
and (ii) some key structural and/or functional differences in major neutralizing immunogenic epitopes. To test
this hypothesis, we propose three specific aims: 1) to identify host and viral determinants of neutralizing antibody
responses combining the RV typing data from multiple cohort studies (n=14) and analysis of titers, time of
appearance and duration of these antibody responses in the COAST children; 2) to determine whether RV-C
genotypes represent unique serotypes or share common epitopes; 3) using human monoclonal antibodies
complexed with RV-C, map major immunogenic epitopes and determine the mechanisms of RV-C antibody
neutralization and cross-neutralization by cryo-EM. These studies will inform the development of a broadly
protective RV-C vaccine that could be of significant ben...

## Key facts

- **NIH application ID:** 10130436
- **Project number:** 5R01AI148707-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Yury A Bochkov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $792,076
- **Award type:** 5
- **Project period:** 2020-03-20 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130436

## Citation

> US National Institutes of Health, RePORTER application 10130436, Mechanisms of Enhanced Neutralizing Antibody Responses to Rhinovirus C (5R01AI148707-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130436. Licensed CC0.

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