# Project I: Discovery and Evaluation of Antibodies and Cocktails

> **NIH NIH U19** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $1,910,034

## Abstract

Abstract – Project I
The overarching goal of the Prometheus consortium is to develop antibody-based prophylactics and
therapeutics against three major groups of Category A priority viruses that pose the highest risk to
national security and public health and cause zoonotic disease—ebolaviruses, the nairovirus Crimean-Congo
hemorrhagic fever virus (CCHFV), the New-World hantaviruses Andes virus (ANDV) and Sin Nombre virus
(SNV), and the Old-World hantavirus Puumula virus (PUUV). No approved treatments are available for any of
these viruses. Given the safety and efficacy of over 50 mAb-based therapies currently available in market for
various diseases, mAbs are a low-risk platform to develop countermeasures for these Category A viruses. The
rapid discovery and development of large numbers of pathogen-specific human monoclonal antibodies (mAbs)
from convalescent and acutely infected donors is the central strength to our platform. Coming from hosts who
have already mounted an effective antibody response, these naturally occurring mAbs are less likely to elicit
tissue cross-reactivity and in vivo toxicity in humans and also obviate the need for chimerization or time-
consuming humanization. Prometheus will use these mAbs as raw material to produce broadly protective
immunotherapeutics that (i) are robust to natural viral genotypic variation; (ii) leverage multi-epitope targeting
and an innovative feature we term RAVE (reciprocal antagonism to viral escape) to enhance potency and resist
escape of viral neutralization; (iii) exploit tuned Fc effector properties for extended in vivo half-life and more
effective elimination of viral particles and infected cells; and (iv) can be directly and rapidly transitioned to
advanced pre-clinical development. Project I will work collaboratively with Project II to identify human mAbs
and oligoclonal mAb cocktails against CCHFV and hantaviruses (SNV, ANDV, and PUUV) with these
properties—pan-ebolavirus lead human mAbs have already been identified by Prometheus members. We will
hand off lead mAbs and cocktails to Core B as candidates for advanced development of therapeutics, and to
Project III for studies aimed at the generation of DNA-encoded mAbs (DMAbs) for prophylactic delivery. In
consultation with the SAC, lead molecules will be evaluated by Core C for protective efficacy in NHP models
of CCHFV and SNV challenge.

## Key facts

- **NIH application ID:** 10335809
- **Project number:** 5U19AI142777-04
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Kartik Chandran
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,910,034
- **Award type:** 5
- **Project period:** 2019-02-14 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335809

## Citation

> US National Institutes of Health, RePORTER application 10335809, Project I: Discovery and Evaluation of Antibodies and Cocktails (5U19AI142777-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10335809. Licensed CC0.

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