# Development of therapeutic pan-Alphavirus human monoclonal antibodies

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $1,829,048

## Abstract

PROJECT SUMMARY
Alphaviruses are positive-strand enveloped RNA viruses of the Togaviridae family that globally cause disease
in humans. As an example, Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes
explosive epidemics in humans of a severe febrile illness characterized by debilitating acute and chronic
polyarthritis. Other arthritogenic alphaviruses (e.g., Ross River (RRV), Mayaro (MAYV), and O’nyong nyong
(ONNV) viruses) are emerging beyond their historical boundaries with outbreaks in Oceania, Africa, and the
Americas. Venezuelan (VEEV) and Eastern (EEEV) equine encephalitis viruses are mosquito-transmitted
alphaviruses with the potential to cause fatal neuroinvasive disease in humans. At present, no antiviral agents
or licensed vaccines exist for the treatment or prevention of any alphavirus infections. The goal of this highly
interactive Project 3 between long-standing collaborators (Diamond, Crowe, Kuhn/Rossmann, Fremont, and
Streblow laboratories) and a new commercial partner (IDBiologics) is to develop Fc-optimized, high potency
pan-alphavirus human mAbs for the prevention and treatment of multiple alphavirus infections in humans.
Our approach is to screen existing and newly generated panels of human mAbs derived from subjects
who were infected or immunized previously with different alphaviruses (CHIKV, RRV, or VEEV) for
extensive cross-reactivity, neutralization, and binding to the surface of infected cells. After a stringent
filtering and Go/No-Go decision process, lead candidate mAbs will be improved by affinity maturation and
optimization of Fc effector functions, and therapeutic potential will be tested in murine models of
alphavirus-induced arthritis and encephalitis. Two secondary goals are to define the structural and
mechanistic correlates of human mAb protection. This information will inform a possible combination mAb
strategy. Subsequently, we will generate CHO cell lines for IND enabling studies, and pairs of optimized
pan-alphavirus mAbs will be tested for therapeutic activity in non-human primate (NHP) models of
alphavirus infection. The proposed research achieves the following CETR RFA goals: (a) Basic
discoveries that are translated into treatments by generating pan-virus mAb therapy with potent protective
efficacy. (b) Since many alphaviruses are emerging and cause large-scale epidemics, this project will
develop a therapy for diseases of unmet clinical need. (c) The work requires an interdisciplinary academic
team and industry partner, which should facilitate the translation into therapeutics. (d) Studies in this
project and CETR provide a platform for the discovery of mAb therapeutics against other viruses. A pan-
alphavirus mAb therapy against the majority of globally relevant alphaviruses will provide an immediate
countermeasure against disease emergence or bioterrorist introduction.

## Key facts

- **NIH application ID:** 10158447
- **Project number:** 5U19AI142790-03
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,829,048
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158447

## Citation

> US National Institutes of Health, RePORTER application 10158447, Development of therapeutic pan-Alphavirus human monoclonal antibodies (5U19AI142790-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10158447. Licensed CC0.

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