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A research team led by scientists from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH has determined how several antibodies induced by the Epstein-Barr virus (EBV), a herpesvirus responsible for infectious mononucleosis and badociated with certain cancers, block cell infection grown in the laboratory. They then used this information to develop new vaccine candidates that, in animals, induced a potent anti-EBV antibody response blocking infection of the cell types involved in EBV-badociated cancers.
Currently, there is no licensed vaccine for EBV. The virus is badociated with certain cancers (nasopharyngeal and gastric) epithelial cells, which form the mucosa of the body surfaces, as well as Burkitt and Hodgkin lymphomas, which are cancers of the B cells of the immune system. Worldwide, approximately 200,000 cases of EBV-badociated cancers occur each year, resulting in 140,000 deaths.
Jeffrey I. Cohen, M.D., and Wei Bu, Ph.D., both of NIAID, led the survey. Previous efforts to develop a vaccine against EBV focused on a viral surface protein, gp350, that the virus uses to enter B cells. However, EBV not only infects B cells, but also epithelial cells lining the mouth and upper throat. These cells are usually infected after contact with the saliva of an individual infected with the EBV virus. The new research helps define the contributions of antibodies neutralizing viruses other than those directed against gp350 on B cells. Among the other findings, the team determined that antibodies directed against viral proteins, called gH / gL complexes , play a major role in inhibiting EBV fusion with epithelial cells.
Scientists have developed two candidate vaccines, one designed to induce anti-gH / gL antibodies on epithelial cells and the other that included gH / gL and another viral protein, gp42. The team tested the vaccines during a series of experiments on mice and monkeys. In both animal models, each of the experimental vaccines induced antibodies that potently inhibited epithelial cell fusion. The vaccine containing gp42 induced more potent B cell fusion inhibitory antibodies than those containing only gH / gL.
In contrast to the EBV gp350 vaccine candidate, which protects only B cells from infection, the candidate vaccines described in the new article have elicited antibodies that may prevent EBV fusion with both epithelial and B cells. , and could thus provide protection independent of the cell type, the authors note. The team plans to further develop one of the vaccine constructs for human trials.
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Material provided by NIH / National Institute of Allergy and Infectious Diseases. Note: Content can be changed for style and length.
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