ReviewThe need and challenges for development of an Epstein-Barr virus 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.
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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.
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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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Cited by (82)
Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus
2020, Cell Reports MedicineCitation Excerpt :In addition to its contribution to oncogenesis, EBV infection is also associated with multiple sclerosis3,4 and rheumatoid arthritis.5 Thus, a safe and effective vaccine that protects against EBV infection and/or pathogenesis would be of clinical benefit, particularly to those in resource-poor settings where the EBV-associated cancer burden is high.6–8 Most effective vaccines elicit antibodies that neutralize infection.9
Identification of multiple potent neutralizing and non-neutralizing antibodies against Epstein-Barr virus gp350 protein with potential for clinical application and as reagents for mapping immunodominant epitopes
2019, VirologyCitation Excerpt :Antibodies, whether elicited in the host naturally or via passive immunization, provide an effective first-line of defense and correlate with protection against viral infection in humans (Iwasaki, 2016). In the past five decades, several immunization studies have indicated that the EBV major immunodominant gp350 is an ideal target for eliciting nAbs in immunized animals and humans (Cohen, 2015, 2018; Cohen et al., 2011, 2013). Although the ectodomain of gp350 (aa 1–841) contains at least seven unique CD21 binding epitopes (Table 1), only one of these epitopes (aa 142–161) has been shown to be capable of eliciting nAbs (Hoffman et al., 1980; Szakonyi et al., 2006; Tanner et al., 1988, 2015; Urquiza et al., 2005).