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Research Highlights
Body’s Own Antibodies May Drive New Strains of HIV
Taken from the Veterans Health Administration Highlights dated March 24, 2003
VA researchers have provided the first detailed look at how human antibodies may actually drive human immunodeficiency virus (HIV) to mutate and escape detection by the immune system. The findings, reported online March 18 in the Proceedings of the National Academy of Sciences, may be key in efforts to develop an effective AIDS vaccine. So far, scientists have been unable to design a vaccine that induces antibodies capable of neutralizing the rapidly mutating virus.
The researchers also found that patients infected with HIV rapidly develop a strong antibody response against the virus. But the same antibodies tasked with recognizing and disabling the germ appear to force its ongoing evolution into new strains that dance around the antibody response and continue to replicate.
“The neutralizing antibodies are exerting a very strong selective pressure on the virus, and the virus is continually mutating to avoid it,” said Richman. “The bad news is that the virus is always staying a step ahead, and the neutralizing antibody response can’t control it.”
They cloned virus from the blood of HIV patients and combined it with a gene that makes luciferase, the light-emitting enzyme found in fireflies. The enzyme helped the researchers track virus replication. The genetically engineered virus from each patient was incubated with antibody-containing plasma from the same patient. This procedure was repeated periodically over 39 months so the researchers could test antibodies from different times against virus from different times.
Most patients developed a high concentration of antibodies to HIV within a few months. The antibodies continually evolved in their ability to recognize different protein shapes on the outer coating of the virus. However the virus consistently evolved faster than the antibody response, developing new protein structures on its surface, so antibodies from previous months’ samples were ineffective in neutralizing new virus from the same patient. The study was the first to track this virus-antibody “cat-and-mouse game” over time.
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