# Human Antibody Cross-Reactivity in Non-Polio Enteroviruses

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $611,746

## Abstract

Project Summary
Manifestations of enterovirus infections are variable, with several severe illnesses such as meningitis, acute
flaccid myelitis (AFM), myocarditis, and neonatal sepsis. Poliovirus vaccines are near perfect at preventing
severe illness by generating strong, circulating antibody responses. However, the polioviruses represent only
three of the more than 100 enteroviruses capable of causing human disease. Recently approved vaccines for
enterovirus A71 are demonstrating that other enterovirus diseases, in this case hand, foot, and mouth disease,
can be prevented by vaccination as well. Our previous work shows that monoclonal antibodies that cross-react
to all clades of enterovirus D68 can protect infected mice from AFM-like disease, and even treat disease after
onset. Rather than try to make 100 vaccines to cover each enterovirus, we propose to understand the qualities
of the human antibody response that could provide cross-reactive immunity across many enteroviruses. With
this knowledge, immunogens can be designed that preserve the B cell epitopes that stimulate cross-reactive
antibodies. We first aim to determine the degree of cross-reactivity of enterovirus antibody responses at a B cell
level. We will complement seroepidemiology studies of hundreds of healthy adults, looking to see what proportion
of them have naturally made antibody responses to the four species of enterovirus, with studies of stimulated
memory B cells from the peripheral blood mononuclear cell compartment. The latter will allow us to see how
many individual B cells in healthy adults produce antibodies that cross-react between enterovirus species, a
knowledge gap with no existing data. Second, we aim to determine the molecular details of enterovirus species
cross-reactivity using human mAbs. We will create human hybridomas that produce monoclonal antibodies
(mAbs), screening and selecting for mAbs that bind to multiple enteroviruses. Antigen-binding fragments of the
mAbs, in complex with virions from all immune-reactive enteroviruses, will be used for cryo-electron microscopy
studies to obtain atomic resolution maps of antibody epitopes, detailing at a molecular level the determinants of
cross-reactivity. Third, we aim to determine mechanisms of antibody action utilizing human primary cell infection
models. As we investigate which stage of the viral life cycle different mAbs disrupt to exert function, using ex
vivo differentiated human epithelial cell cultures will preserve the natural cell surface receptors used by viruses
during in vivo human infection. The knowledge gained from these studies will allow detailed understanding of
how cross-reactive antibodies bind to enteroviruses and how they function. In turn, the mAbs can be used to
functionally validate that candidate immunogens preserve these cross-reactive B cell epitopes. Finally, some
mAbs could later have potential for direct use in humans, either as prophylactic or therapeutic agents. This is an
especia...

## Key facts

- **NIH application ID:** 10796795
- **Project number:** 5R01AI169461-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Matthew R Vogt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $611,746
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796795

## Citation

> US National Institutes of Health, RePORTER application 10796795, Human Antibody Cross-Reactivity in Non-Polio Enteroviruses (5R01AI169461-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10796795. Licensed CC0.

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