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Vaccines for the 21st Century: A Tool for Decisionmaking
but only 2 of the 10 who got gp350 were infected. Much has been done in terms of designing gp350 to be produced in the cells and working on a strategy for clarification in high quantities. Abnormal viral response in the absence of antibodies to fusion protein is a concern.
T-cell epitope vaccines are also being investigated, because researchers have identified so many of the CTL epitopes that are critical for EBV infections. Experiments with SCID mice indicate that it is possible to transfer CTLs and thereby control viral proliferations. Such a vaccine might provide prophylactic protection for transplant recipients and (in combination with gp350) in nasopharyngeal carcinoma. Tumors may not express key antigens, or viral functions may impair peptide presentation.
Ultimately, however, the goal would be to make a genetically altered EBV vaccine. This would be essential to protect against EBV-related malignancies such as Burkitt’s lymphoma and nasopharyngeal carcinoma, where the infection would have to be eliminated to prevent the disease. As detailed above, many of the necessary steps have been taken in this direction. Many people are infected with both type 1 and type 2 EBV, suggesting that wild-type infection is not protective.
Animal Models. Animal models are somewhat limited. Cotton-top tamarinds develop lymphomas when EBV is injected parenterally, and they can be protected with gp350 vaccine. SCID-human chimeric mice also develop EBV lymphoproliferative diseases, and can be protected with transferred CTLs; but they may not be very useful for evaluating vaccines because of transient T-cell function and the absence of appropriate lymphokine synthesis.
A new and promising prototype is a mouse EBV homologue, although it might be more similar to herpes saimiri. You can induce infection by internasal inoculation, and the mice develop lymphoid proliferations that have some similarities to EBV infection. However, the most encouraging animal model is a rhesus EBV that is highly homologous to EBV, and has identical patterns of mucosal infection and disease. Also, SIV-infected animals develop lymphomas. This may be the ideal system to test a genetically altered EBV virus.
In response to questions from the audience, Dr. Raab-Traub added the following:
No research is being done to analyze the mucosal infection or to induce mucosal immune response. There have been anecdotal reports of defective viral genomes in some seronegative subjects. These genomes, which lack the transforming EBV genes that generated immunoglobulin-A response in saliva, might offer some protection.
100 percent of infected B-lymphocytes become immortalized.
Recombinant gp350 vaccine should be ready for testing in a small seronegative population soon. It would be effective against both type 1 and type 2 EBV.