Philadelphia -- Three Wistar Institute immunologists have been awarded grants to support their development of vaccines against diseases that attack the mucous membranes. Principal Investigator, Hildegund Ertl, MD, was awarded a grant by the Mary L. Smith Charitable Lead Trust for her research on HIV-1 vaccines. Anthony Wlazlo, PhD, and Dariusz Kowalczyk, MD, researchers in Dr. Ertl's laboratory, earned fellowships from the Cancer Research Foundation of America for their development of vaccines against human papilloma viruses (HPV).
Because the mucous membranes are protected by an independent immune system, Dr. Ertl suspects they are not adequately protected by systemic vaccines. Consequently, she and her Wistar research team are designing vaccines that target the mucosal immune system.
To successfully prevent HIV-1, explains Dr. Ertl, a combination vaccine is needed to induce neutralizing antibodies at the site of virus entry, usually the genital mucosa, and to trigger the production of killer T cells. Immunologists have yet to determine if it is possible to do both simultaneously. The immune system typically generates either a Th1 response to disease, which activates killer T cells, or a Th2 response, which promotes the development of B cells that secrete antibodies at mucosal surfaces. It is a challenge, says Dr. Ertl, to develop a vaccine that can simultaneously induce both. Dr. Ertl's findings will also be useful to scientists in other research centers exploring similar approaches
At the same time, other scientists in Dr. Ertl's laboratory are developing vaccines against HPV, a group of viruses known to cause cervical cancer, the second most common malignancy in women. Rather than treating the cancer, explains Dr. Ertl, the key to controlling HPV is through a vaccine that prevents the infection. The researchers' goal is to produce a strong and enduring mucosal immunity by neutralizing antibodies that, in model systems, prevent infections with papilloma viruses.
It has been shown that antibodies aimed at the L1 antigen, which is the capsid protein of papilloma viruses, can induce protective immunity to infection and prevent the development of tumors. This activity is being examined in depth by Dr. Kowalczyk. His preliminary data show that the mucosal immune response to the target antigen can be induced by an intranasal immunization with an adenoviral recombinant.
Dr. Wlazlo is simultaneously studying oncoproteins expressed by HPV strains 16 and 18, which are known to cause cancerous transformations in the cells. Dr. Wlazlo is exploring the feasibility of using these oncoproteins as vaccine antigens for the treatment of cervical cancer. HPV-16 does not usually cause acute disease immediately after infection, but can, after years of latency, contribute to the development of cervical cancer.
The Wistar Institute, established in 1892, was the first independent medical research facility in the country. For more than 100 years, Wistar scientists have been making history and improving world health through their development of vaccines for diseases that include rabies, German measles, infantile gastroenteritis (rotavirus), and cytomegalovirus; discovery of molecules such as interleukin-12, which are helping the immune system fight bacteria, parasites, viruses and cancer; and location of genes that contribute to the development of diseases that include breast, lung and prostate cancer. Wistar is a National Cancer Institute Cancer Center.