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Antibody evolution could guide HIV vaccine development

Sat, 04/06/2013 - 3:25pm

The evolution of the viral protein (green) from 14 weeks through 100 weeks post-transmission is compared with the maturation of the human antibody. Image: Los Alamos National LaboratoryObserving the evolution of a particular type of antibody in an infected HIV-1 patient has provided insights that will enable vaccination strategies that mimic the actual antibody development within the body. Spearheaded by Duke University, the multi-institution study included analysis from Los Alamos National Laboratory and used high-energy X-rays from the Advanced Photon Source at Argonne National Laboratory.

The kind of antibody studied is called a broadly cross-reactive neutralizing antibody, and details of its generation could provide a blueprint for effective vaccination, according to the study’s authors. In a paper published online in Nature titled Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus, the team reported on the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection.

The observations trace the co-evolution of the virus and antibodies, ultimately leading to the development of a strain of the potent antibodies in this subject, and they could provide insights into strategies to elicit similar antibodies by vaccination.

Patients early in HIV-1 infection have primarily a single "founder" form of the virus that has been strong enough to infect the patient, even though the population in the originating patient is usually far more diverse and contains a wide variety of HIV mutations. Once the founder virus is involved in the new patient’s system, the surrounding environment stimulates the HIV to mutate and form a unique, tailored population of virus that is specific to the individual.

The team - including Bette Korber, Peter Hraber, and S. Gnanakaran of Los Alamos National Laboratory, led by Barton Haynes of the Duke University School of Medicine, with colleagues at Boston University, the National Institutes of Health, and other institutions as part of a large collaboration—showed that broadly neutralizing antibodies developed only after the population of viruses in the individual had matured and become more diverse.

"Our hope is that a vaccine based on the series of HIV variants that evolved within this subject, that were together capable of stimulating this potent broad antibody response in his natural infection, may enable triggering similar protective antibody responses in vaccines," says Korber, leader of the Los Alamos team.

Peter Kwong and Tongqing Zhou of the National Institutes of Health and the Center for Vaccine Immunology-Immunogen Discovery led the X-ray studies of the virus and antibodies with the goal of creating an atom-by-atom picture of the co-evolution of the antibody CH103 and the HIV-1 virus. This picture of what induces the body to create antibodies that can neutralize more than one strain of the virus is crucial to creating a vaccine that can stay ahead of the virus as it mutates in the body. The intensely focused X-rays of the APS were used to hone in on a small portion of the epitope protein in the HIV virus that is recognized by the body’s immune system and the broadly neutralizing antibody it triggers to develop. This reaction can only be seen using X-rays like those at the APS because the scientists need to look at an ultra-small portion—about 20 microns in size—of a protein cluster. For comparison, it would take 2,000 microns to equal the diameter of the head of a pin.

Source: Argonne National Laboratory

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