# Development of a Preclinical Assay to Predict Efficacy of Ricin Toxin Subunit Vaccines

> **NIH NIH R01** · WADSWORTH CENTER · 2020 · $519,830

## Abstract

Project Summary
Ricin toxin (RT) is classified by the National Institute of Allergy and Infectious Diseases (NIAID) as an
Emerging Infectious Disease Priority Pathogen. NIAID and the Department of Defense are each
supporting efforts to develop an effective RT subunit vaccine. A major roadblock to developing RT
vaccines is the absence of a functional preclinical assay to predict efficacy in humans. While it is well
established that immunity to RT is mediated by antibodies, the immune response against ricin toxin A
subunit (RTA)-based antigens consists predominantly (>90%) of non-neutralizing antibodies. Indeed,
detailed functional and structural analyses of RTA-specific murine and camelid monoclonal antibodies
(MAbs) has revealed that toxin-neutralizing activity (TNA) is associated a very limited number of B
epitope “clusters” on the surface of RTA. Conventional cell-based cytotoxicity assays are not
sufficiently sensitive to detect the small fraction of toxin-neutralizing antibodies responsible for
protective immunity. From the standpoint of vaccine development, it is critical to develop a more
sensitive and direct assay to measure serum antibodies against the key protective epitopes.
Therefore, the goal of this program is to develop a preclinical ELISA-based competition assay that will
predict the efficacy of RT subunit vaccines in humans. Aim 1 will e stablish a prototype competition
ELISA-based assay that identifies a serum antibody profile associated with protective immunity
against RT. Aim 2 will qualify the competition ELISA-based assay in a NHP model to define antibody
profile that is associated with protection against aerosolized RT. Finally, Aim 3 will validate the
competition ELISA using human sera from Phase I and II studies. As part of this program we will
establish the link between MAb competition and protective immunity, with the expectation that the
ability to measure epitope-specific neutralizing antibody responses will constitute a major advance in
assessing the efficacy of candidate RT subunit vaccines in humans.

## Key facts

- **NIH application ID:** 9913443
- **Project number:** 5R01AI125190-05
- **Recipient organization:** WADSWORTH CENTER
- **Principal Investigator:** Nicholas J. Mantis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $519,830
- **Award type:** 5
- **Project period:** 2016-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913443

## Citation

> US National Institutes of Health, RePORTER application 9913443, Development of a Preclinical Assay to Predict Efficacy of Ricin Toxin Subunit Vaccines (5R01AI125190-05). Retrieved via MORVS 2026-10-10 from https://api.morvs.ai/grant/nih/9913443. Licensed CC0.

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