# Project II: Biologics Engineering and Antibody Mechanism of Action

> **NIH NIH U19** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $1,890,899

## Abstract

The rapid discovery of human monoclonal antibodies (mAbs) that arise during natural viral
infection is central to the Prometheus consortium for developing immunoprophylactic and
therapeutic medical countermeasures (MCMs). Our Center of Excellence for Translational
Research will focus on developing MCMs for three groups of NIAID Category A priority
pathogens (ebolaviruses, Crimean-Congo hemorrhagic fever virus, and hantaviruses).
Ebolaviruses, members of the family Filoviridae, cause severe hemorrhagic fever in humans and
non-human primates, with human case-fatality rates of up to 90%. As demonstrated by the 2013–
2016 epidemic of Ebola virus disease in West Africa, ebolaviruses pose a significant public health
threat. Crimean-Congo hemorrhagic fever virus is a member of the Bunyaviridae family and
induces fatal hemorrhaging in up to 50% of human infections. Hantaviruses also belong to the
Bunyaviridae family, and infections are associated with over 150,000 cases of disease annually
with case-fatality rates >30%. Given the disease severity caused by these viruses, MCMs are
urgently needed.
 The protective efficacy of hyperimmune serum in animal models and humans strongly
suggests that human infection and disease by these groups of viruses will be amenable to
treatment with mAb-based therapeutics and prophylactics. Project II will facilitate mAb discovery
efforts in Project I via the development of molecular tools (Aim 1) required to isolate and
characterize candidate therapeutic mAbs from human survivors. Our focus will be on the
generation of novel recombinant antigens and BSL-2 viral surrogates to use as probes in single B-
cell sorting experiments. These biologics are also vital to the characterization process (Aim 2) that
will define mAb epitopes, competition groups, structures, and mechanisms of action, as well as future
product assay development in Core B. The data generated by Project II, combined with potency and
synergy data from Project I, will allow for a streamlined and mechanistically informed down-selection
of the most promising candidate mAbs and mAb combinations for in depth Fc-effector function
analyses and optimization (Aim 3) prior to in vivo evaluation of leads by Core C. Project II will also
be involved in finalizing the optimal lead immunoprophylactic mAbs to advance in Project III and
immunotherapeutic mAbs to enter advanced development within Core B.

## Key facts

- **NIH application ID:** 9873000
- **Project number:** 5U19AI142777-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Kartik Chandran
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,890,899
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873000

## Citation

> US National Institutes of Health, RePORTER application 9873000, Project II: Biologics Engineering and Antibody Mechanism of Action (5U19AI142777-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9873000. Licensed CC0.

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