November 13, 2002
|Researchers at the Houston VA Medical Center are working to develop a genetic vaccine against HIV, the virus that causes AIDS. "An oral genetic vaccine has many potential advantages," said Dr. Frank Orson, a staff physician in allergy and immunology at the HVAMC. "It would be easy to transport, should require no refrigeration, and won't need trained medical personnel or sophisticated medical equipment for vaccine administration."
Photo by Shawn D. James, HVAMC Media Section
HOUSTON, TX - The fight against HIV/AIDS needs a shot in the arm, or better yet, an oral vaccine.
Researchers at the Houston VA Medical Center (HVAMC) are working to develop a genetic vaccine against HIV, the virus that causes AIDS. The virus is spreading throughout the world with 15,000 new cases appearing each day. A majority of those cases are in developing countries.
"With the easy travel existing between most countries, the high frequency of infection in many countries, and the long period after infection before symptoms appear, HIV is going to be a threat to everyone in future generations," said Dr. Frank Orson, a staff physician in allergy and immunology at the HVAMC. "An effective vaccine is the only way to combat this epidemic in the long run."
Through a VA Merit Review grant, Orson and other HVAMC researchers are utilizing animal studies to aid efforts to develop a DNA-based HIV vaccine.
"Our primary focus is on development of an oral vaccine that would provide immune protection in the genital mucosa, the entry site for most HIV infections," said Orson, who is also an associate professor of medicine, immunology, and molecular virology and microbiology at Baylor College of Medicine. "If successful, this type of immune protection would block sexual transmission of the virus."
Genetic immunization uses a circular piece of DNA called a plasmid that includes the genetic instructions for producing a specific protein, in this case a protein from an HIV strain.
"The plasmid is the delivery vehicle for the vaccine. When inserted in a cell, it tells the cell to produce the protein." Orson said. "When the cell produces the protein, it is recognized as foreign and the immune system is triggered."
Key in the immune defense system are cytotoxic T lymphocytes, known as CTLs. "The CTLs are especially good at smoking out virus-infected cells and killing them," Orson said. "Once activated, they can even kill newly infected cells before they have a chance to produce the virus and that stops the spread of the infection."
This type of oral vaccine will initially stimulate both antibody and CTL responses in the mucosa of the gastrointestinal tract, but the benefit will spill over into other mucosal tissues.
Vaccine delivery by aerosol to the lung is under investigation as another means of stimulating the mucosal system. Whatever means of delivery, the vaccine will need to be effective for many HIV strains.
"With HIV, there is a constant shift in the structure of these proteins because the virus makes random changes to its genetic code every time it reproduces in a newly infected cell," Orson said. "If we can design the vaccine to handle multiple variations, we will be able to achieve better protection against the moving target of HIV."
Orson's VA research team is utilizing mice to investigate the immune response and is collaborating with researchers at Texas A&M University in studies of feline immunodeficiency virus.
"An oral genetic vaccine has many potential advantages," Orson said. "It would be easy to transport, should require no refrigeration, and won't need trained medical personnel or sophisticated medical equipment for vaccine administration."
Genetic vaccine delivery systems for HIV also have implications for research in vaccines against other conditions such as allergic disease, influenza, pneumonia and cancer, as well as vaccines against biological warfare microorganisms.
Supported with more than $12 million annually, research conducted by HVAMC scientists and physicians ensures veterans access to cutting-edge medical and health care technology.
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Point of Contact: VHAHOU Public Affairs04/21/04 08:25