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Researchers Hone New Approach to Rabies Vaccine


(PHILADELPHIA) Researchers at the Jefferson Vaccine Center, report significant progress in the "holy grail" of rabies research — development of a single-dose vaccine. Currently, a time-consuming and expensive course of preventative antibody followed by four-five doses of immune-boosting rabies vaccines is needed, after exposure to a potentially infected animal.

In two studies published in the Journal of Virology, the latest published June 12, the research team found that their experimental vaccine induces an immune response that had not been known to play a role in rabies immunity. The vaccine, produced in the laboratory of James McGettigan, PhD, harnesses the first line of defense against a wide range of viruses. Dr. McGettigan's novel vaccine is the first to take advantage of the power of this protective defense against rabies virus.

He says a new approach to rabies treatment in sorely needed.

"Two-thirds of the world's population lives in regions where rabies is endemic. A person — usually a child — dies of rabies every 20 minutes. More than 15 million people worldwide receive multi-dose post-exposure vaccines, costing about $1 billion annually to prevent rabies infections in humans," Dr. McGettigan says.

"Rabies is considered a neglected global zoonotic infectious disease. Therefore, efforts to develop a single-dose human vaccine for use in both developing and industrialized countries are critically needed," he says.

Dr. McGettigan and his laboratory colleagues, led by Corin Dorfmeier, MS, sought to understand how they could induce a rapid induction of specific cells in the immune system known as B cells, which is required for successful treatment, especially in cases when treatment is delayed after exposure.

They developed a vaccine based on a replication-deficient rabies virus that lacks a key gene called the matrix (M) gene that induced rabies immunity rapidly.

"Typically, B cells require ‘help' from another cell type of the immune system, called CD4+ T cells. T cells promote effective B cell responses to secrete antibodies against rabies virus, therefore, preventing rabies from causing damage," Dr. McGettigan says. "However, the process by which CD4 T cells help B cells to make antibodies takes time, which may limit its effectiveness to treat rabies after infection, especially in cases when treatment is delayed."

Dr. McGettigan shows that their matrix gene-deleted rabies virus-based vaccine bypasses the need for T cells for the development of effective B cells.

He says their vaccine induces an antibody subtype, called IgM, which was not known to play a role in rabies immunity.

"The speed by which IgM is induced may help reduce the need for multi-dose vaccine strategies," he says. "More importantly, vaccine-induced IgM may help to reduce the need for the initial dose of protective antibodies — rabies immune globulin — which is expensive and in short supply in developing countries."

Dr. McGettigan's group is currently working on strategies that further exploit their finding, by enhancing the T cell-independent, IgM, antibody response.

Dr. McGettigan's work in the two studies was funded by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (R01AI079211).