# Defining Critical Sites of Vulnerability and Correlates of Protection to Kaposi Sarcoma Associated Herpesvirus to Inform Vaccine Design

> **NIH NIH U01** · FRED HUTCHINSON CANCER CENTER · 2024 · $767,691

## Abstract

PROJECT SUMMARY
Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi sarcoma (KS), one of
the most common malignancies in people living with HIV worldwide. KSHV also causes primary effusion
lymphoma (PEL) and multicentric Castleman disease (KSHV-MCD). Infection is common in sub-Saharan Africa
and often occurs early in childhood, while in the western hemisphere, infection is rare in the general population
but more frequent in men who have sex with men. A vaccine that prevents KSHV infection and/or associated
morbidity and mortality represents a critical unmet need. However, the types of immune responses a vaccine
would need to elicit have not been well defined. Here we will seek to identify the relevant antigenic targets and
specific epitopes targeted by KSHV-neutralizing antibodies and to establish the ability of neutralizing antibodies
to protect against KSHV infection in a small animal model. To do this, we will leverage a large pre-collected
repository of serum and PBMC samples from KSHV+ participants with and without KS disease to characterize
the neutralizing antibody response to KSHV. We will produce recombinant KSHV glycoproteins that will be used
to deplete serum binding antibodies and assess their contribution to the polyclonal serum neutralizing response.
In parallel, we will isolate neutralizing monoclonal antibodies from KSHV+ PBMC samples and carry out in-depth
structure-function analyses to identify critical sites of vulnerability on KSHV glycoproteins. Lastly, we will evaluate
the ability of neutralizing KSHV monoclonal antibodies to prevent infection in a humanized mouse model of
KSHV infection. Our studies will define the relevant antigens and epitopes targeted by neutralizing antibodies
that arise from natural KSHV infection and thus inform the design and development of KSHV vaccines. Moreover
in vivo protection from KSHV infection will establish critical proof of concept that a KSHV vaccine should seek to
elicit neutralizing antibodies.

## Key facts

- **NIH application ID:** 11003468
- **Project number:** 1U01CA295050-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Jim Boonyaratanakornkit
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $767,691
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11003468

## Citation

> US National Institutes of Health, RePORTER application 11003468, Defining Critical Sites of Vulnerability and Correlates of Protection to Kaposi Sarcoma Associated Herpesvirus to Inform Vaccine Design (1U01CA295050-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11003468. Licensed CC0.

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