A small antibody fragment that is highly effective in neutralizing the human immunodeficiency virus (HIV) by preventing the virus from entering cells has been identified by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).
This finding may provide insight into the development of new treatments against HIV and other viruses, hopefully in the not too distant future. The study appears online Oct. 20, 2008, in Proceedings of the National Academy of Sciences.
Treating HIV-infected individuals is difficult because the virus is able to mutate and become resistant to antiretroviral drugs. "In the United States, it is estimated that more than 50 percent of patients who are receiving antiretroviral therapy for their HIV infection carry strains of the virus that are resistant to treatment with at least one of the currently available antiretroviral drugs," said NCI Director John E. Niederhuber, M.D. "The development of new drugs against HIV is an urgent public health need."
Antibodies are large proteins naturally produced by the immune system to help fight disease-causing foreign invaders, such as viruses and bacteria. Although the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies, characterized by slightly different tip structures, to exist and bind to different targets, known as antigens. Previous research has shown that reducing antibodies to the smallest independently functional fragment, known as a variable domain, can extend their utility as therapeutic agents. These fragments, called domain antibodies (dAbs), retain the variable tip structure and, therefore, the antigen-binding specificity of the parent antibody. Because of their small size, they are able to access targets that cannot be reached by much larger, whole antibodies.
In an earlier study, the researchers identified a unique antibody, called m0, while screening a large library of antibodies directed against the HIV protein, Env (also known as gp120). The library contained the variable portions of antibodies that can bind to Env antigens. "We found an antibody fragment that exhibited the ability to neutralize HIV and had properties that allowed us to construct a novel library containing dAbs directed against HIV," said Dimiter S. Dimitrov, Ph.D., of NCI's Center for Cancer Research.