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Novel vaccine concept developed by scientists at the Wistar Institute
Date:1/31/2008

ein D binds to a receptor molecule called HVEM (herpes virus entry mediator) on antigen-presenting cells. By locking onto the HVEM receptor, glycoprotein D prevents HVEM from binding to another molecule called BTLA on T and B lymphocytes white blood cells that attack disease-causing pathogens.

Binding between HVEM and BTLA is the first step in an inhibitory signaling pathway that reduces the immune systems response to the presence of a virus. Blocking this inhibitory pathway allows the body to mount a stronger immune response by generating more antigen-specific CD8+ T cells to attack cells infected with the virus.

The researchers found that fusing HIV and HPV antigens to glycoprotein D enhances the immune response to those antigens. Mice injected with vaccines that included antigens fused to glycoprotein D generated more virus-killing CD8+ T cells than mice injected with the same vaccines and antigens, but without the glycoprotein D carrier protein.

Researchers also inoculated identical strains of laboratory mice with vaccines containing genes for the cancer-causing proteins E7, E6 and E5 from the HPV-16 virus. One group of animals received HPV-16 genes spliced into the genetic code for glycoprotein D; another group received the same antigens without glycoprotein D. Ten to 14 days later, both groups of animals were injected with a fast-growing tumor cell line that normally generates extensive tumors in mice within 14 days.

Mice that received vaccines with the glycoprotein D-antigen combination were fully protected against cancer, says Wistars Marcio Lasaro, Ph.D., lead author of the study. However, mice inoculated with vaccines containing the same HPV-16 genes, but without glycoprotein D, developed tumors after being inoculated with the same tumor cell line.

Its important to point out that the molecules we targeted in mice are similar to those in humans, and all the basic in-vitro studies in the paper were done with hu
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Contact: Abbey Porter
aporter@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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