GAITHERSBURG, Md.— GenVec Inc. recently amended and extended its existing collaborative agreement with the PATH Malaria Vaccine Initiative (MVI). This will provide up to $750,000 in additional funding through the end of 2007 to continue advancing a new multivalent malaria vaccine toward preclinical evaluation prior to the production of cGMP materials that will be required for human clinical evaluation.
The Naval Medical Research Center (NMRC), charged with protecting the health and safety of U.S. Navy and Marine Corps personnel, had done the principal work in sequencing the malaria genome and, about four years ago, agreed to work with GenVec under a separate Collaborative Research and Development Agreement (CRADA). NMRC scientists provided GenVec with optimized malaria genes used in the adenovector vaccines and will perform preclinical evaluations. To date, these combined efforts have resulted in one anti-malaria vaccine reaching Phase 1 clinical trials.
The multivalent vaccine was developed under a multiyear CRADA with MVI currently worth up to $3.9 million, for the production and evaluation of adenovirus vectors containing genes for up to five malaria antigens. MVI is a global program established initially with a grant from the Bill & Melinda Gates Foundation. PATH, MVI's Seattle-based parent, is an international non-profit with a mission to create "sustainable, culturally relevant solutions enabling communities worldwide to break longstanding cycles of poor health."
GenVec has been involved with vaccines for more than five years, including development projects to combat foot-and-mouth disease, seasonal and pandemic influenza and HIV, says Dr. Rick King, senior vice president of research. The company's adenovector technology delivers multiple antigens in a single vaccine with the prospect of thereby enhancing immunological efficiency. This multivalent vaccine contains the genes for up to five malaria antigens from different stages of the parasite's life cycle. Three are expressed from a single adenovector and target the liver stage of the disease while two additional antigens are expressed from a second adenovector and target the blood stage of the disease; all are thought to be important in preventing or limiting the severity of malaria.
Dr. Joseph Bruder, GenVec's director of vector and vaccine programs, states that including multiple antigens in one adenovirus vector lowers cost by increasing efficiency. Lower vaccine production costs will be of major importance to developing nations where malaria is prevalent.
"If you have three antigens in one vaccine it can be produced for roughly a third of the cost of producing three vaccines, each with one antigen. Also, you are delivering more genes in fewer particles which should produce a well-tolerated dose," Bruder says.
Also, the company notes that many malaria experts believe a vaccine containing more than one malaria antigen will be necessary to adequately protect against the disease.
All of GenVec's drug development work is based on adenovector technology and is patent-protected, King points out. GenVec's IP includes formulation and production know-how, and ongoing improvement of its adenovirus vector technology.
"You have to have a way to produce the adenovector you want," King states. This is done by removing genes that cause the virus to replicate. These "multiple deficient" adenoviruses particles are then inserted so cells can replicate but the inserted virus cannot.
GenVec's lead product, TNFerade is currently in Phase II/III clinical trials in locally advanced pancreatic cancer; Phase II studies are in progress in rectal cancer and melanoma; and Phase I/II studies are in progress in head and neck cancer. The TNFerade vector is remarkably similar to the vaccine vector, Dr. King and Dr. Bruder agree. The inserted gene encodes human necrosis factor. When the drug is injected into a tumor, cells express TNF to destroy cancer cells.