Elsevier

Vaccine

Volume 31, Supplement 2, 18 April 2013, Pages B194-B196
Vaccine

Review
The need and challenges for development of an Epstein-Barr virus vaccine

https://doi.org/10.1016/j.vaccine.2012.09.041Get rights and content

Abstract

Epstein-Barr virus (EBV) is the major cause of infectious mononucleosis and is associated with several malignancies including nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and lymphoma after organ or stem cell transplant. A candidate vaccine containing soluble EBV glycoprotein gp350 protected cottontop tamarins from EBV lymphoma after challenge with EBV. In the only phase 2 trial of an EBV vaccine in humans, soluble gp350 in alum and monophosphoryl lipid A adjuvant reduced the rate of infectious mononucleosis in EBV seronegative adults, but did not affect the rate of EBV infection. A peptide vaccine corresponding to EBV latency proteins has been tested in a small number of adults to prevent infectious mononucleosis. Some of the barriers to development of an EBV vaccine include (a) whether viral proteins in addition to gp350 would be more effective for preventing mononucleosis or EBV malignancies, (b) the difficulty of performing clinical trials to prevent EBV associated malignancies in the absence of good surrogate markers for tumor development, and the long period of time between primary EBV infection and development of many EBV tumors, (c) the lack of knowledge of immune correlates for protection against EBV infection and disease, (d) the limitations in animal models to study protection against EBV infection and disease, and (e) the need for additional information on the economic and societal burden of infectious mononucleosis to assess the cost-benefit of a prophylactic vaccine.

Highlights

EBV results in over 120,000 cases of infectious mononucleosis in the US each year. ► EBV is associated with about 200,000 cases of cancer worldwide each year. ► An EBV subunit vaccine reduced the rate of infectious mononucleosis in a trial. ► More information is needed on surrogate markers to predict EBV associated cancers. ► Further studies are needed to identify immune correlates for an EBV vaccine.

Section snippets

Background

Epstein-Barr virus (EBV) causes over 90% of cases of infectious mononucleosis (IM) in developed countries [1] with cytomegalovirus as the second most common cause. EBV is usually spread from oral secretions and the virus infects resting B cells in the oropharynx or epithelial cells which in turn infect B cells. Infection early in life is usually asymptomatic or results in nonspecific symptoms, while infection of adolescents or young adults can result in IM. IM is usually a self-limited disease

Barriers/problems

While EBV gp350 appears to be a valid immunogen for a vaccine to prevent IM, it is unknown whether a vaccine with additional EBV antigens might be more effective in preventing IM or virus infection. EBV encodes a number of other glycoproteins that elicit neutralizing antibodies. EBV also encodes a very large number of proteins that are targets of CD4 and CD8 T cells [17]. It is not clear what combination viral proteins would be needed for a vaccine to prevent EBV-associated malignancies. The

Concrete actions/recommendations

A recent meeting at the National Institutes of Health proposed a number of recommendations for future research and EBV vaccine studies [21]. Some of these are outlined below.

  • There is a need to determine the burden of IM in developed countries. Epidemiologic studies should be performed to better determine the cost-benefit of a prophylactic vaccine for IM.

  • A phase 3 study of gp350, with or without additional viral proteins, should be performed to determine for certain if gp350 definitively reduces

Conflict of interest

Edward Mocarski is a paid consultant in the area of EBV vaccines for MedImmune, LLC. Lawrence Corey holds shares in Immune Design Corporation which has supplied an adjuvant which may be used in a candidate EBV vaccine developed by MedImmune, LLC. The other authors do not have conflicts of interest.

Acknowledgement

Jeffrey Cohen is supported by the intramural research program of the National Institute of Allergy and Infectious Diseases.

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