# Discovery & characterization of human monoclonal antibodies targeting multiple arthritogenic alphaviruses

> **NIH NIH F30** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $48,070

## Abstract

Project Summary
 Alphaviruses are enveloped, positive sense single-stranded RNA viruses, which include several
important human pathogens. Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses
that cause human rheumatic disease and include chikungunya virus (CHIKV) and Mayaro virus (MAYV).
Symptomatic infection is characterized by fever, rash, myalgia, as well as both acute and chronic polyarthralgia
that can persist for months to years after infection. More severe manifestations of alphaviral disease –
including hemorrhage, encephalopathy and mortality – have been reported. These viruses cause endemic
disease as well as large, sporadic epidemics worldwide. Currently, there are no approved vaccines or anti-viral
therapies for the prevention or treatment of alphavirus infection; therefore, the development of new therapeutic
strategies targeting one or multiple arthritogenic alphaviruses is of substantial interest.
 A number of potently neutralizing CHIKV monoclonal antibodies (mAbs) have been described, but
currently the only broadly neutralizing alphavirus mAbs that have been reported are murine. Thus, the extent to
which the human antibody response elicits broadly-neutralizing mAbs following alphavirus infection, and which
epitope(s) such mAbs may target, remains unknown. To address this question, this proposal seeks to expand
our knowledge of the neutralizing antibody response to alphaviruses by systematically investigating cross-
reactive antibodies from CHIKV-infected patients. Towards this end, we have used single B cell sorting to
isolate a large panel of MAYV-reactive mAbs from CHIKV patients in the convalescent phase. We will study
the reactivity and neutralization profiles of these mAbs against related arthitogenic alphaviruses (Aim 1). We
will then biochemically determine the requirements of neutralization (Aim 2) and elucidate the mechanism of
mAb inhibition (Aim 3). These studies will contribute to our fundamental understanding of how the adaptive
immune system combats infection by arthritogenic alphaviruses and may aid the development of novel mAb-
based treatments and vaccines.

## Key facts

- **NIH application ID:** 10445303
- **Project number:** 5F30AI150055-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Ryan J Malonis
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $48,070
- **Award type:** 5
- **Project period:** 2020-07-22 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445303

## Citation

> US National Institutes of Health, RePORTER application 10445303, Discovery & characterization of human monoclonal antibodies targeting multiple arthritogenic alphaviruses (5F30AI150055-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10445303. Licensed CC0.

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