06 February 2008

The herpes virus will help in the creation of antiviral vaccines

Creating antiviral vaccines is a very difficult task, because if the vaccine is not effective enough, the virus will spread through the body faster than the immune system can destroy it; at the same time, too strong action of the vaccine can lead to the death of the body itself.

A new approach to creating vaccines proposed by researchers at the Wistar Institute of Anatomy and Biology (Philadelphia, Pennsylvania), working under the guidance of Dr. Hildegund Ertl, can solve this problem. The secret lies in the use of the herpes simplex virus protein – glycoprotein D, which blocks a specific receptor molecule of the surface of antigen-presenting cells (APC). These specialized cells capture foreign proteins entering the body and prepare them for presentation to cytotoxic T-lymphocytes.

Activated in this way, T-lymphocytes begin to destroy all virus-infected or malignant cells they encounter. At the same time, they synthesize signaling molecules – cytokines that prevent the development of excessive immune reactions. Glycoprotein D of the herpes virus blocks one of three inhibitory signals.

Glycoprotein D is part of the viral envelope and is expressed on the surface of cells infected with the herpes simplex virus. It binds to a molecule called the herpes virus entry mediator (HVEM) on the surface of antigen-presenting cells and prevents its interaction with the surface receptors of T- and B-lymphocytes, which is the first stage of the mechanism suppressing the antiviral immune response. Blocking this inhibitory mechanism allows the body to trigger a more pronounced immune response by forming more virus-specific CD8+ T lymphocytes.

The authors demonstrated that their proposed vectors, formed as a result of the fusion of the glycoprotein D gene and genes encoding viral antigenic sequences, significantly enhances the immune system's response to these antigens both in cell culture and when administered to laboratory mice. In the experiments, the genes of HIV proteins and human papillomavirus type 16 associated with cervical cancer were used.

According to the head of the work, the results obtained are especially important for the development of an HIV vaccine/AIDS. The main problem faced by the developers of vaccines against this disease is that the drugs effective in experiments on mice and primates turn out to be too toxic in doses necessary for successful human vaccination. The authors believe that glycoprotein D will help to overcome this barrier, because its use can significantly reduce the dosage of the vaccine.

The researchers are planning further work to study the mechanisms that ensure the effectiveness of their proposed method. If successful in future animal trials, they hope to conduct clinical trials of vaccines against HIV and papillomavirus, which the institute's specialists are already working on.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily.

06.02.2008

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