Researchers Gain New Insights Into One Way That Antibodies Can Develop
A team of researchers has identified one way the human body can develop powerful antibodies to protect it against the AIDS virus, offering a new lead in the quest for a vaccine.
The findings, the latest in a series of advances in AIDS research in the past few years, are significant because scientists were able to establish a link between a change in the virus after infection and the formulation of the antibodies that fight it.
Scientists just over three years ago identified two potent antibodies that could target most of the thousands of strains of HIV, the virus that causes AIDS. Since then, dozens more "broadly neutralizing antibodies," as they are called, have been identified.
But researchers haven't known how they develop - critical information they need to create a vaccine, which has been one of modern medicine's greatest challenges and has remained elusive more than 30 years after the epidemic erupted.
In a study published online in the journal Nature Medicine Sunday, researchers from the Centre for the AIDS Programme of Research in South Africa discovered a key change in the outer coating of the HIV virus that had enabled two HIV-infected women to develop broadly neutralizing antibodies.
The HIV virus is famously elusive, evolving and changing constantly - even over the course of a week within a single patient. But the piece of the virus on which the change occurred in the women is common across many HIV strains, and the antibodies one of them developed were able to kill up to 88% of HIV strains from around the world. Released by the immune system, antibodies stick to the surface of a virus and prevent it from entering a cell.
The study is "an important step in trying to understand just how these broadly neutralizing antibodies evolve," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, the arm of the National Institutes of Health that oversees AIDS research and helped fund the study.
The researchers followed the two women for years, making it possible to figure out when and how the change in the virus occurred that allowed them to develop the antibodies, Dr. Fauci said.
The study represents "a key advance in the vaccine field," said Wayne Koff, chief scientific officer of the International AIDS Vaccine Initiative, which helps develop and promote vaccines. "It builds on a lot of advances in the last three or four years" that have brought about a "renaissance" in the field, he said.
About 34.2 million people were living with HIV in 2011, and 1.7 million died, according to the Joint United Nations Programme on HIV/AIDS.
"We were able to go back to our freezers and pull out specimens," said Salim Abdool Karim, a prominent AIDS researcher and director of the consortium that did the study. At about six to nine months after infection, he said, a "glycan," or sugar, changed positions on the HIV virus's outer coating, forcing the women's immune systems to mount a response to a new piece of the virus.
Researchers tracked one of the women starting in April 2005, when she was 36 years old and enrolled in a consortium study on acute HIV infection. The woman, from Durban, South Africa, developed HIV infection in February 2006, despite having a stable partner, Dr. Abdool Karim said. Within three years of infection, her body was producing antibodies capable of neutralizing 88% of a large panel of HIV viruses against which it was tested.
The second woman, enrolled in July 2007 in another HIV study, became infected with the HIV virus in June 2008. Her antibodies neutralized 46% of a panel of HIV viruses to which they were exposed two years after infection.
The researchers weren't able to test further to see if her antibodies would become more powerful and kill more strains of the virus, though. The woman developed tuberculosis, for which HIV-infected patients are at increased risk. It evolved into an extreme form of drug-resistant tuberculosis, and she died in June 2011, Dr. Abdool Karim said.
Still, because the woman demonstrated the same change in the virus, "we would expect within the next year she would have attained a similar response" as the first subject, Dr. Abdool Karim said.
The virus change that prompted the women's immune systems to produce the antibodies is probably just one of several ways antibodies develop, scientists say. Other broadly neutralizing antibodies target other parts of the HIV virus.
A vaccine remains far off. One problem is that the subjects of the study developed their broadly neutralizing antibodies only after a change in the virus - not the form that initially infected them.
Still, clinical trials on initial vaccine candidates based on research on broadly neutralizing antibodies will begin within the next two or three years, Dr. Koff said.
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