# Characterization of broadly neutralizing antibodies against JC virus

> **NIH NIH K02** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $144,245

## Abstract

Dr. Chen Sabrina Tan, an Infectious Diseases physician at Beth Israel Deaconess Medical Center, seeks to
establish herself as an independent physician-scientist conducting translational research in Neuro Virology and
Immunology. A K02 award will provide the protected time and support necessary for her to accomplish the
following goals in studying antibody responses against JC virus, the etiologic agent of Progressive Multifocal
Leukoencephalopathy (PML): 1) characterize neutralizing antibodies against JCV: 2) determine if
complement participates in JCV immune response/neutralization; and 3) identify and clone broadly
neutralizing antibodies as potential therapies for PML, the disease caused by JCV. To accomplish these,
Dr. Tan has assembled a group of excellent advisors and collaborators. Drs. Michael Seaman and Joern
Schmitz, long-term members of Center for Virology and Vaccine Research (CVVR), where Dr. Tan’s lab is
located, will provide advice and guidance on antibody neutralization assays. Dr. Schmitz, Director of the Flow
Cytometry Core Facilities, will also guide B cell sorting and isolation. Dr. Anne Nicholson-Weller, a member of
the Division of Infectious Diseases, is advising Dr. Tan on complement studies. Dr. Keith Reimann, Senior
Director at MassBiologics, University of Massachusetts, will advise on cloning and construction of the
recombinant broadly neutralizing monoclonal antibodies.
PML remains an often fatal opportunistic infectious disease of the central nervous system (CNS) in patients
with HIV and those with multiple sclerosis treated with immune-modulatory medications such as natalizumab or
dimethyl-fumarate. Since pre-existing anti-JCV antibodies are detected in most PML patients, their role in
controlling CNS infection has been questioned. However, recent work has revealed that single amino acid
alterations in the JCV VP1 capsid protein could change glycosylation and possibly alter antibody binding. Thus,
antibody control of JCV needs to be better studied. Our overall goal is to better understand and harness the
antibody immune response for prevention and treatment of PML. The central hypothesis is that JCV-specific
neutralizing antibodies control JCV proliferation in the blood and brain. We posit that characterization of
antibody-mediated responses against JCV in the CNS and isolation of broadly neutralizing antibodies against
JCV has the potential to translate into a new class of therapeutics. We will test this hypothesis by pursuing two
specific aims: Aim 1. To characterize the function and mechanism of JCV-neutralizing antibodies in
patients. Aim 2. Identify broadly neutralizing antibodies against JCV.
The proposed studies will further develop Dr. Tan’s career as an independent physician-scientist in antibody-
mediated responses against viruses in the CNS, generate the necessary preliminary data to apply for and
obtain an R01 by year 3, and create a novel therapy for PML.

## Key facts

- **NIH application ID:** 9699552
- **Project number:** 5K02NS097146-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Chen Sabrina Tan
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $144,245
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9699552

## Citation

> US National Institutes of Health, RePORTER application 9699552, Characterization of broadly neutralizing antibodies against JC virus (5K02NS097146-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9699552. Licensed CC0.

---

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