Will Old Weapon Work Against HIV?

Researchers from the Wistar Institute report that a human adenovirus called AdHu26, once thought uncommon, is not so rare, after all. This could be bad news for scientists eager to use engineered AdHu26 human adenoviruses as vaccines against HIV and other diseases.

In the approach, adenoviruses, which commonly cause respiratory-tract infections, are rendered relatively harmless before being used as vectors to deliver genes from pathogens, which then stimulate the body to generate an immune response. Yet studies show that a viral vector may be less effective if the vector is based on a type common in a population because humans will have previously developed immunity to it.

"AdHu26 is considered by some to be rare in nature and thus there should be less preexisting immunity. Hildegund Ertl [at Wistar] is claiming this is incorrect, at least for certain human populations," says Mark J. Newman, Ph.D., vice president of Research and Development at GeoVax Labs, headquartered in Smyrna, Georgia. In its quest for an HIV vaccine, GeoVax has turned for help to a poxvirus vector called modified vaccinia ankara, originally developed as a smallpox vaccine.

"Since we no longer administer smallpox vaccine except to the military and a select group of first responders for the potential use of smallpox by bioterrorists and smallpox has been eliminated from the human population, the vast majority of people are not being exposed to vaccinia viruses, of which MVA is one," Newman says. "Thus there is a lack of preexisting immunity, at least in people who were born after 1971 when the universal use of the smallpox vaccine was discontinued."

Because of the difficulty raising antibodies that are capable of totally blocking natural HIV infections, the GeoVax vaccine approach has focused on raising cellular immune responses in addition to antibodies, which together should be better able to block and control the infections than either can alone.

The company's vaccine proteins, which are inactivated proteins from HIV, are expressed in cells of the vaccinated person following administration of genetically engineered DNA vectored vaccines and live viral vector MVA vaccines. MVA was chosen, in part, because of its safety features but also because a sufficient amount of HIV genetic material can be inserted which supports the production of virus-like particles in cells.

These particles mimic immature HIV cells and present the viral proteins to the immune system in the correct conformation inducing both cellular immune responses and antibodies. Testing using preclinical nonhuman primate models documented the utility of these vectors for inducing the desired types of immune responses. The company believes this novel approach may well succeed where the use of approaches that induce other types of immune responses may fail.