Pitt professor’s research to help create AIDS vaccine

When he first joined Dr. Robert Montelaro’s graduate research team, Surojit Sarkar said he… When he first joined Dr. Robert Montelaro’s graduate research team, Surojit Sarkar said he couldn’t find a project in the labs that interested him. So he asked to start a completely new project based on the comprehensive exam proposal he had written for graduate school. Though this might have been a bold move for a brand new member of a research group, Montelaro gave him the green light and some funding to get started.

Four years later, Montelaro is turning Sarkar’s idea into a way to develop a more effective AIDS vaccine.

The American Foundation for AIDS Research, or amfAR, has recently granted Montelaro, professor of molecular genetics and biochemistry at the Pitt School of Medicine, $90,000 to study the effects of the formation of a sugar coating around the surface, or viral envelope, of HIV, and the ways this coating affects the host’s immune response.

The information the study will add to current knowledge of HIV will aid the collaborative efforts of other universities, biotech companies and the National Institute of Health to construct a successful vaccine.

Sarkar’s theory, the basis for the new study, stems from the fact that the HIV protein envelope, or outer layer, is covered with a dense shield of sugar molecules. Though HIV will often mutate to evade the immune attacks of its host, the virus undergoes glycosylation, or the addition these sugar molecules, in all its forms, indicating that this feature is important to its survival.

Sarkar initially studied a case of Simian Immunodeficiency Virus, which belongs to the family of lentiviruses along with HIV, at Pitt’s infectious diseases primate facility.

He then compared his observations with data about HIV glycosylation to theorize that the sugar coating covers nearly all of the proteins on the surface of the virus. The helper T white blood cells, which use those proteins to recognize the virus and develop an effective response, are unable to get the necessary information they need to form a successful attack.

Sarkar explained this by saying that sugar is already present in the human body and therefore is not considered a threat by the immune system.

In order to prove that glycosylation in HIV hinders immune response, the researchers will use enzymes to completely strip the virus of its sugar coating, or deglycosylize it. Then they will infect two genetically similar sets of mice with the virus and compare the mouse response to the deglycosylized virus with its response to the sugarcoated one.

They hope to determine which particular types of white blood cells are recognizing and responding most strongly to the uncoated virus, which would be shown by how much the cell divides. If the experiment provides enough data to substantiate the theory, they hope to start testing monkey immune responses to deglycosylized HIV.

By taking this approach in their study, Montelaro said that they’re not looking to actually modify the proteins in the virus, but rather figure out ways to prime the immune system. He described these “priming immunizations” as vaccines that would put small, weakened parts of the virus’s exposed viral envelope into the bloodstream, which would allow the white blood cells to recognize them and learn how to fight them in the future.

AmfAR, the country’s leading nonprofit organization in support of AIDS research, chose the proposal as one of four out of 188 candidates for funding this year.”

Montelaro explained that amfAR provides the seed money to get small projects going.

“We would use that seed money to bring it along to the National Institute of Health, which requires more data,” he said.

The National Institute of Health, a federal bureau that promotes biomedical research, can provide five-year grants worth between $500,000 and $800,000, which could help fund more extensive examinations of deglycosylized HIV activity in higher animals.

“It was great that we got this money from amfAR because it allows us to express our ideas,” Sarkar said. “It’s a really good idea to start with something small but significant, and that’s what we did.”