Vaccine Aims to Give HIV/AIDS a Shot of DNA

The fight against HIV/AIDS is about to get a shot in the arm, so to speak.

Researchers at the Houston VA Medical Center 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 in developing countries.

“With the ease of travel between most countries, the high frequency of infection in many countries, and the long incubation period before symptoms appear, HIV is a threat to future generations,” said Frank Orson, M.D., a staff physician in allergy and immunology at the HVAMC. “A vaccine is the only way to combat this epidemic in the long run.”

Through a VA Merit Review grant, Orson and other researchers at the hospital are utilizing animal studies to aid efforts in developing 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.”

Cytotoxic T lymphocytes, known as CTLs, are key in the immune defense system.

“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.”

The oral vaccine will initially stimulate both antibody and CTL responses in the mucous tissue lining 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. However, whatever means of delivery is used, the vaccine will need to be effective for multiple HIV strains.

“With HIV, there is a constant shift in protein structure, because the virus makes random changes to its genetic code every time it reproduces in a newly infected cell,” Orson said. “We are striving to design the vaccine to handle multiple variations, in order 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 allergies, influenza, pneumonia and cancer, as well as vaccines against biological warfare microorganisms.

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©2006 Texas Medical Center

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