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.