# A multivalent prophylactic and therapeutic vaccine against EBV infection and EBV-associated malignancies

> **NIH NIH R56** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $858,605

## Abstract

ABSTRACT: Epstein-Barr virus (EBV) represents a major global health problem, as it is associated with
infectious mononucleosis in adolescents and >200,000 pediatric and adult cancer cases worldwide each year.
Despite the high morbidity and mortality associated with EBV infection, there is no licensed prophylactic EBV
vaccine. Thus, a safe and effective EBV prophylactic vaccine is urgently needed. To date, no vaccine
candidate has elicited neutralizing antibodies (nAbs) to completely block EBV infection in vivo. Approaches to
EBV vaccine development have been limited in part by the oncogenic potential of the viral genome and a lack
of animal models to test vaccine candidates. This proposed project will use a novel strategy to develop a safe
and effective vaccine candidate that incorporates up to five EBV glycoproteins into a single Epstein-Barr virus-
like particle (EBV-LP). The EBV glycoproteins gp350, gB, gp42, and gH/gL complex, which are essential for
EBV attachment, fusion, and entry into host cells, are attractive targets for provoking a humoral/antibody-
mediated response. Our group and others have shown that antibodies to these glycoproteins neutralize viral
infection in vitro and in vivo. Thus, their inclusion is critical for developing an effective prophylactic vaccine that
protects against viral infection. To our knowledge, this combination of EBV antigens has not been tested in pre-
clinical or clinical trials. We will generate EBV-LPs containing combinations of up to five glycoproteins using
modified vaccinia Ankara virus. We will determine the efficacy of the EBV-LPs to generate nAb responses in
wild-type mice, then test the ability of these antibodies to neutralize >90% of EBV infection of human epithelial
and B cells in vitro and to prevent infection of human B cells in vivo in a humanized mouse model (Aim 1).
Because EBV is human-tropic, we will use the EBV-homologous rhesus lymphocryptovirus (rhLCV) as a
surrogate virus to study vaccine efficacy in vivo in rhesus macaques (RM), considered the most relevant
animal model that recapitulates key features of human EBV infection. Importantly, RM orally inoculated with
rhLCV exhibit acute symptoms and viral shedding similar to EBV+ humans, as well as development of
lymphoma after persistent infection under immunosuppression. We will evaluate the ability of our EBV-LP-
based or analogous rhLCV-LP-based vaccines to elicit nAbs that can prevent or limit infection, with no/low EBV
DNA in blood, splenocytes, or lymph nodes, and absence of EBV+ cancer in immunocompetent and
immunocompromised RM, compared to well-characterized EBV gp350-based vaccines (Aim 2). Our central
hypothesis is that EBV-LPs/rhLCV-LPs will generate protective anti-EBV/rhLCV glycoprotein nAb responses
to prevent EBV/rhLCV infection in vitro and in vivo. We expect our approach to provide a path to an
investigational new drug application for a prophylactic EBV vaccine. We will also define, for the first time, the
minimum E...

## Key facts

- **NIH application ID:** 10247243
- **Project number:** 1R56AI148295-01A1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Javier Gordon Ogembo
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $858,605
- **Award type:** 1
- **Project period:** 2020-09-08 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247243

## Citation

> US National Institutes of Health, RePORTER application 10247243, A multivalent prophylactic and therapeutic vaccine against EBV infection and EBV-associated malignancies (1R56AI148295-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247243. Licensed CC0.

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