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The Battle Between HIV And Antibodies: why the virus gets the upper hand - 2003-03-20

When the human body is infected with HIV, the virus that causes AIDS, the immune system responds with antibodies that are designed to prevent or fight off infection. However, new research shows why HIV manages to stay one step ahead of the body’s attempts to eliminate it.

The job of so-called “neutralizing” antibodies is to recognize and disable invading germs. And studies find that once a person is infected with HIV, the body has a strong antibody response. But those same antibodies that are supposed to protect the body may actually help HIV evolve into new strains that continue to reproduce. This finding, while discouraging at first light, may hold the key to developing an AIDS vaccine.

The antibody study was conducted by a team led by Dr. Douglas Richman, a virologist with the Veterans Affairs San Diego Health Care System and the University of California.

He says when the antibodies begin to attack HIV, they are met with an overwhelming replicating response from the virus. The virus mutates or changes and the body’s first line of defense has a difficult time defending against all the variations.

Dr. Richman says, "It makes mistakes. I mean that’s what mutations are. They’re mistakes in the genetic materials for each progeny (offspring) virus. But it makes so many viruses that it makes almost every possible mistake in the period of a day. And the mistakes that are successful in evading the immune response then become the predominant viruses. I mean its Darwinian evolution magnified a million fold in terms of the rate."

Dr. Richman says while the antibodies themselves evolve to recognize different versions of HIV, they can not do it fast enough.

He says, "What’s really quite remarkable is how quickly the virus continues to change. As each individual generates a neutralizing antibody response to the new virus, the virus is always staying one step ahead."

He says the virus replicates as many as one hundred billion “new particles every day.” Despite the body’s immune system being one step behind HIV, scientists are taking an optimistic view.

Dr. Richman says, "The optimist would say that because this neutralizing antibody response is exerting such a strong selective pressure, it’s proof that it’s an effective selective force. And so that it might be very useful for prophylaxis - that is, prevention of new infections. Although it’s not very effective in dealing with an ongoing infection."

In other words, scientists are looking into whether antibodies can be engineered to recognize many different strains of HIV at the same time. If those engineered antibodies are present at time of infection – such as through a vaccine – they could offer better protection.

Researchers, however, agree that for an AIDS vaccine to work it will have to activate two parts of the immune system: antibodies and killer white blood cells, which provide longer-term protection. A number of vaccines relating to the white blood cells are in clinical trials. Nevertheless, Dr. Richman says an effective AIDS vaccine is still five to ten years away. He calls the effort the “Holy Grail of vaccine design.”