By Daniela Kenzelmann
Cervical cancer can be caused by a virus called the human papillomaviruses (HPV). That is why the development of a preventive HPV vaccine has been a breakthrough achievement. However the economics limit the availability of the vaccine to many parts of the world. That is why American and Italian researchers are looking at producing the HPV vaccine in plants.
Cervical cancer is one of the leading cancer-related causes of death in woman worldwide, particularly in developing countries where regular diagnostic screening is not common. It is known that cervical cancer can be caused by infection with certain types of human papilloma viruses (HPV), and these infections are widespread in sexually active women. Recently, two pharmaceutical companies, Merck and Glaxo-Smith-Kline have developed effective HPV vaccines which promise to help reduce the risk of cervical cancer.

However, this type of vaccine will only prevent new HPV infections, because the target of the vaccine is a protein on the surface of the virus, which is only accessible for the immune system before infection. This means that women who already have an HPV infection will not benefit from this vaccine.

That is why effort is underway to produce vaccines to viral proteins that are visible to the immune system once HPV has already infected a cell. These proteins, called E5, E6 and E7 are also responsible for reprogramming the host cells in such a way that they can become cancerous.

Such a therapeutic vaccine would enable the immune system to eliminate an existing HPV infection and even fight cells that have already turned cancerous. Vaccines based on the E7 protein have been successfully tested in animal models and are now in an advanced stage of clinical trials.

Dr. Yusibov, executive director of the Fraunhofer Center for Molecular Biotechnolgy in Newark, and Italian collaborators have tested plant-produced E7 as a vaccine in an animal model. Previous experiments have already demonstrated that an E7-vaccine produced in plants triggers immune responses in mice. Moreover, pretreatment with the vaccine protected most of the mice from tumor formation after injection of tumor cells which produce the E7 target protein.

In their new publication, Dr. Yusibov and collaborators have found a more efficient way to produce the E7 protein in plants. This is achieved by incorporating the E7 protein into a bacterial protein called LicKM. The use of this patented, carrier-protein ensures that the E7 protein can be produced in high amounts and increases its stability.

Additionally, the researchers found that the LicKM-E7 fusion protein provoked a stronger immune response in mice compared to E7 alone. In the cancer model, tumor protection was also enhanced in mice vaccinated with the LicKM-E7 vaccine.

Dr. Yusibov's work confirms that the E7 protein is a suitable target for a therapeutic cervical cancer vaccine, and it demonstrates that such a vaccine can be economically produced in plants. This would be particularly beneficial for developing countries, where cervical cancer is the main cause of cancer deaths. Plant-based technologies would allow production of an affordable vaccine to protect women who have no access to routine screenings for cervical cancer.



www.fmi.ch / www.checkbiotech.org