# Rational Vaccine Design to prevent HIV-Associated Lymphoma

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $664,754

## Abstract

PROJECT SUMMARY/ABSTRACT
 Relative to the general population, HIV-infected individuals have a 60–200-fold higher relative risk to
develop Non-Hodgkin's Lymphomas, including plasmablastic lymphoma, primary central nervous system
lymphoma, primary effusion lymphoma and diffuse large B-cell lymphoma. They also have an 8–10-fold higher
relative risk to develop Hodgkin's Lymphoma compared to uninfected individuals. Many of these malignancies
are driven by Epstein-Barr virus (EBV) and result from poor immune control of the virus driven by HIV-
dependent immune dysfunction. Thus, a safe and effective vaccine that prevents EBV infection and eliminates
the EBV-associated component of risk could have a significant clinical benefit in resource-poor areas where
HIV-1 is endemic. The correlate of protection for most successful viral vaccines is neutralizing antibodies.
 Previously, our lab isolated the first anti-EBV mAb that could potently neutralize infection of both B cells
and epithelial cells. We further demonstrated that passive transfer of AMMO1 protected both humanized mice
and rhesus macaques from experimental EBV infection. These results strongly suggest that antibodies are
important for, if not sufficient to protect against EBV infection, and that a prophylactic vaccine should seek to
elicit high titers of AMMO1-like antibodies. To this end, we developed and tested several gH/gL vaccines. All
gH/gL vaccines were strongly immunogenic, but they only showed partial protection against experimental EBV
infection in humanized mice and macaques. Epitope mapping studies revealed that vaccine-elicited gH/gL
antibodies targeting the AMMO1 epitope were subdominant and rare, while antibodies targeting other non-
neutralizing epitopes on gH/gL were immunodominant.
 The goal of this proposal is to obtain a high-resolution antigenic landscape of the gH/gL glycoprotein to
define the most critical sites of vulnerability. We will then use this this information to employ structure guided
EBV vaccine design intended to immunofocus the antibody response onto protective epitopes like the one
targeted by AMMO1, and evaluate their ability to protect against EBV challenge in humanized mice and
macaques.

## Key facts

- **NIH application ID:** 10839116
- **Project number:** 1R01CA285227-01A1
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Andrew McGuire
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $664,754
- **Award type:** 1
- **Project period:** 2024-02-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839116

## Citation

> US National Institutes of Health, RePORTER application 10839116, Rational Vaccine Design to prevent HIV-Associated Lymphoma (1R01CA285227-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10839116. Licensed CC0.

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