# Delineating the mechanism and inhibitory capacity of CMV neutralizing antibodies

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $253,463

## Abstract

Research Summary:
Human cytomegalovirus (CMV) is a -herpesvirus that can cause morbidity and mortality in immuno-
compromised individuals. Following primary infection, which is usually benign in immunocompetent individuals,
CMV establishes latency and can periodically reactivate. CMV disease can manifest mild to severe disease
condition in immunocompromised individuals. In newborns, CMV-associated neurological disorders represent
the leading cause of birth defects affecting infants worldwide. Additionally, CMV causes gastrointestinal
disorders, pneumonia, CMV syndrome, and end-organ disease in transplant recipients and is linked to early
vascular damage resulting from infection of endothelial cells and macrophages. Ganciclovir is commonly used
as an anti-CMV drug, but it has limitations including poor oral bioavailability, dose-related toxicity, selection of
drug resistant viral mutants, and is precluded for use in pregnant women. The numerous shortcomings of the
current treatment to prevent or treat CMV disease warrant the development of more potent and safer anti-CMV
therapies. Immunoglobulin-based therapy is a promising pharmaceutical option for anti-CMV therapy based on
its specificity, safety profile, and pharmacological activity. The overall objective of the grant is to evaluate the
effectiveness of CMV neutralizing monoclonal antibodies (mAbs) to inhibit virus dissemination. We hypothesize
that CMV neutralizing mAbs that block cell-free infections have the potential to effectively inhibit virus
dissemination. To test this hypothesis, we will complete the following specific aims: 1) Delineate the inhibitory
capacity of CMV neutralizing mAbs to determine the mechanism of action of neutralizing mAbs targeting the
envelope proteins. And 2) Characterize neutralizing mAbs that effectively inhibit virus dissemination using in
vitro and in vivo model systems. We plan to determine the mAbs that effectively inhibit viral dissemination
using physiological-like assays including cell-associated spread of patient derived clinical strains, viral spread
from latently infected cells, and an in vivo animal model. Importantly, we are expecting to define the critical
steps of virus entry that are amenable to therapeutic intervention and identify mAbs as potential therapeutic to
limit CMV-associated diseases.

## Key facts

- **NIH application ID:** 9995918
- **Project number:** 1R21AI147632-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Domenico Tortorella
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $253,463
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995918

## Citation

> US National Institutes of Health, RePORTER application 9995918, Delineating the mechanism and inhibitory capacity of CMV neutralizing antibodies (1R21AI147632-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995918. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*