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Algorithm Identifies HIV Antibodies For Vaccine Design

X-ray crystallography image showing antibody in green binding to vulnerable area (yellow) of HIV-1 virus (red). Courtesy: Structural Biology Section, NIAID

X-ray crystallography image showing antibody in green binding to vulnerable area (yellow) of HIV-1 virus (red). Courtesy: Structural Biology Section, NIAID

Biologists at National Institute of Allergy and Infectious Diseases (NIAID), part of National Institutes of Health, developed a mathematical model to highlight antibodies that neutralize viruses in people with HIV, which can help design a vaccine against HIV infection. The team from NIAID’s Vaccine Research Center, with colleagues from Columbia University and research institutes in South Africa, describe their findings in this week’s issue of the journal Science (paid subscription required).

Development of a vaccine to prevent HIV infections would greatly benefit from a way of identifying the antibodies that can neutralize the viruses found in the majority of HIV strains. Up to now, however, researchers and clinicians lacked a method for quickly and reliably analyzing blood samples for these antibodies or the way they interact with affected viruses. Current methods for understanding the binding process between antibodies and viruses also tend to be laborious and require relatively large amounts of a patient’s blood.

The team led by Vaccine Research Center acting director John Mascola and structural biology chief Peter Kwong focused on the HIV-1 type, which is the most common and pathogenic type of HIV, but also has four areas known to be sensitive to broadly neutralizing antibodies. Blood serum — the part of blood without cells or clotting factors — containing these antibodies likewise shows neutralization patterns that are easier to identify.

The researchers analyzed these neutralization patterns by studying the interactions between the antibodies and 34 different strains from the HIV-1 type. That analysis yielded a set of 30 unique virus-neutralization patterns. Some of these fingerprints were so different from others that the researchers could further identify antibodies that targeted specific areas on a virus’s surface. Antibodies aiming at the same part of the virus were found to have similar fingerprints.

With these unique virus-neutralization patterns, the researchers devised an algorithm to identify the neutralizing antibodies in the blood serum of people with HIV. The team tested the algorithm with 24 volunteers infected with the HIV-1 virus. The results showed the algorithm’s method matched at least one of two published neutralization maps of macaque monkeys infected with human HIV. The researchers also validated their technique against antibodies isolated from the blood serum of two donors using  current testing methods.

The new analytical process is expected to speed development of an HIV vaccine by providing specific targets — the viral neutralizing antibodies — for the vaccine to stimulate. The new method also requires less blood and returns results more quickly than current techniques.

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