# Project 5: Multi-scale development and evaluation of broadly-effective vaccines against picornaviruses with pandemic potential

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $3,478,173

## Abstract

Project Summary/Abstract – Project 5: Multi-scale development and evaluation of broadly-effective
vaccines against picornaviruses with pandemic potential
Picornaviruses are the most common causes of viral illnesses worldwide. Within the picornavirus family of
positive-strand RNA viruses, enteroviruses such as poliovirus, coxsackievirus, enterovirus A71 (EV-A71), and
enterovirus D68 (EV-D68) have the potential to produce devastating disease sequelae in humans, including
paralytic poliomyelitis, cardiomyopathy, pancreatitis, encephalitis, meningitis, and acute flaccid myelitis (AFM).
Surprisingly, the only enterovirus vaccines with U.S. FDA approval are the highly successful inactivated and
attenuated vaccines against poliovirus. In addition, there are no approved antiviral drugs to successfully treat
enterovirus infections despite their considerable pandemic potential. The availability of phylogenetically-
conserved, structure-based design approaches across a large number of related enteroviruses provides a range
of new opportunities to generate a comprehensive panel of mRNA- and protein-based vaccine candidates to
combat infection by these important human pathogens. The experimental approach for this project involves the
testing of mRNA and protein/adjuvant vaccine candidates using in vitro virus culture and animal
challenge/pathogenesis models. The proposed project will also explore novel approaches to vaccine design and
construction that leverage the unique features of picornavirus biology to generate lead strategies that may prove
broadly effective. The proposal will also employ state-of-the-art murine models for evaluating vaccine efficacy
and protection from disease. This standardized series of in vivo models will provide a unique opportunity to
compare efficacy of vaccine responses across different enterovirus serotypes and species and identify the most
promising candidates for advancement to large animal models. Collectively, the breadth of experiments proposed
will create a validated workflow for developing and testing new vaccines that are designed to provide
broad protection against multiple different known pathogenic picornaviruses. Importantly, when
combined with the other cores and projects in this application, this approach is predicted to allow the
rapid development and preclinical evaluation of vaccines and nanobody therapeutics to any new
picornavirus that emerges and represents a significant public health concern.

## Key facts

- **NIH application ID:** 10863346
- **Project number:** 1U19AI181968-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Bert L Semler
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,478,173
- **Award type:** 1
- **Project period:** 2024-08-20 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10863346

## Citation

> US National Institutes of Health, RePORTER application 10863346, Project 5: Multi-scale development and evaluation of broadly-effective vaccines against picornaviruses with pandemic potential (1U19AI181968-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10863346. Licensed CC0.

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