/ 14 November 2006

Antibodies destroy HIV-infected cells

Antibodies that are active against HIV proteins may provide a successful strategy against infection, investigators in Germany and the United States report in the medical journal PLoS Medicine.

In test tube experiments, an antibody that attacks the outer HIV envelope glycoprotein 41, which was labeled with a radioactive isotope so its movement could be detected, killed white blood cells infected with HIV, report Ekaterina Dadachova, of the Albert Einstein College of Medicine in Bronx, New York, and her colleagues. The same antibody selectively killed HIV-infected cells in two mouse experiments of human HIV infection, without causing toxic side effects.

This type of ”radioimmunotherapy could provide a novel treatment option that may hasten the day when curative regimens are available for the eradication of HIV-1 infections,” the team writes.

A similar strategy is already used to treat some cancers, the researchers point out. Dadachova’s group also has shown that radioimmunotherapy can treat fungal and bacterial infections by targeting the microbes themselves.

The researchers suggest that this tactic would be even more effective in treating HIV infection, because ”the majority of long-lived infected cellular targets are (white blood cells), which are among the most radiosensitive cells in the body.”

Moreover, this type of treatment may be particularly beneficial for eliminating persistent reservoirs of infected cells.

Their most successful candidate is an antibody against the HIV envelope transmembrane protein gp41. In test tube experiments, treatment led to the killing of two types of infected human cells — T cells and peripheral blood mononuclear cells.

To test this antibody in a living organism, the research team used immune deficient mice that had HIV-infected mononuclear cells in their spleens. One hour after infection, the researchers injected the labelled antibody.

By increasing the dose, the authors were able to almost completely eliminate the HIV-infected cells. The radio labelled antibody was also effective in destroying HIV-infected human thymus cells in mice.

Dadachova and her associates suggest that radioimmunotherapy would be effective immediately after HIV exposure or for infections caused by multi-drug resistant HIV. They add that combination therapy with HAART, or using a ”cocktail of monoclonal antibodies” may be another effective strategy.

In a press release from the Albert Einstein College of Medicine, senior author Dr Arturo Casadevall remarks that ”this work introduces a new approach for treating many viral infections, from hepatitis C to Ebola”. – Reuters