# Refocusing the immune response from structural to conserved non-structural proteins as a novel vaccination approach for inducing broad anti-enterovirus protection

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $228,233

## Abstract

Multiple enteroviruses are associated with life-threatening and economically important diseases, yet the
licensed vaccines are only available against poliovirus and enterovirus 71. The antigenic diversity of
enterovirus capsids restricts the protective efficacy of vaccines only to antigenically very similar viruses. Even
for closely related polioviruses, the three serotypes must be covered by separate vaccine products. In most
cases such targeted vaccine development approach cannot even be implemented, either because of the
biological constraints, such as antigenic diversity of rhinoviruses, or economic unattractiveness of developing
vaccines against viruses only sporadically associated with severe pathologies, such as Coxsackie viruses
linked to the development of diabetes, myocarditis and dilated cardiomyopathy. Thus, in spite of a pressing
need for an effective vaccine coverage of existing and emerging enterovirus threats, the current
vaccine development strategies focused on inducing neutralizing antibodies against capsid antigens
are intrinsically incapable of delivering products meeting this demand.
Yet, unlike the antigenically diverse capsids, the non-structural proteins of these viruses feature a significant
degree of conservation, so that the elements of the replication machinery are essentially interchangeable
among diverse enteroviruses, resulting in the phenomenon of extensive recombination of enterovirus
genomes.
In this application we present data to support, and propose to explore the hypothesis that posits the following:
Antigenically diverse enteroviral capsids are immuno-dominant antigens which divert the development
of immune response away from the conserved non-structural proteins. Consequently, by removing the
input of the capsid proteins, the development of the immune response to enterovirus infection can be rerouted
towards the conserved membrane-associated proteins of the replication machinery. likely resulting in: 1.
Refocusing the protection mechanism from that based mostly on neutralizing antibodies to the one
mediated by T-cell cytotoxicity, and 2. Providing protection against broad spectrum of enteroviruses.

## Key facts

- **NIH application ID:** 10254302
- **Project number:** 5R21AI153976-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** George A. Belov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $228,233
- **Award type:** 5
- **Project period:** 2020-09-04 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254302

## Citation

> US National Institutes of Health, RePORTER application 10254302, Refocusing the immune response from structural to conserved non-structural proteins as a novel vaccination approach for inducing broad anti-enterovirus protection (5R21AI153976-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10254302. Licensed CC0.

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