Antibody-based drug could hinder progression

Research points to potential of this approach

No matter how far-reaching a viral epidemic is, some people don’t become infected when exposed to the virus, and this may be due to their innate immunity. Researchers who are studying how and why this happens are paving the way for creation of an antibody-based medication that will prevent or slow the progression of HIV to AIDS.

"The idea is that there are certain species-specific innate characteristics of immunologic system materials which allow for a spontaneous control of infectious diseases," says Toby C. Rodman, PhD, professor emeritus at Cornell University Medical Center and an HIV researcher in New York City. Rodman’s research into innate immunity and HIV infection receives grant funding from The Institute for Human Genetics and Biochemistry of Geneva, Switzerland.

Rodman and colleagues, who published their results in the August issue of Experimental Hematology, have used human umbilical cord blood to obtain monoclonal antibody secreting cells. They’ve identified these cells as innate human immune system factors with specific disease-resistant characteristics. "One idea is there must be antibodies that are reactive with certain infectious agents, certain proteins, or infectious agents, and those antibodies are capable of exerting a certain amount of protection," Rodman says.

Specifically, the investigators found evidence that IgM antibodies that are specifically reactive with the HIV Tat protein are innate human immune factors, and these are capable of restricting certain mechanisms of HIV pathogenicity attributed to the Tat protein. "I looked at a series of specimens taken from HIV-positive people and found those antibodies that maintained constant titer in [HIV-negative] people declined after infection of HIV," Rodman says.

Then investigators showed that the same IgM antibodies inhibited a well-defined pathogenic activity of the Tat protein, which kills many different kinds of cells, but particularly CD4 T-cells. "We showed in vitro that these antibodies that were in circulating blood of HIV-negative people could inhibit the decline of CD4 T-cells in HIV-positive people," Rodman says. "Finally, we showed that the cells that make these antibodies are present in cord blood, so they’re definitely innate antibodies."

Since the study was published, there has been a great deal of interest in the potential commercial use of the findings, Rodman says. For example, scientists might be able to develop a way to use human umbilical cord blood to isolate cells for the production of human monoclonal antibodies that would be used therapeutically. Rodman says the model has a strong potential for efficacy, with little obvious potential for side effects.