From Scripps: “Getting closer to an HIV Vaccine”

Scripps
Scripps Research Institute

January 2016
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Authors of the new paper [no paper reference in article] included (left to right) James Voss, Raiees Andrabi, Dennis Burton, Bryan Briney and Chi-Hui Liang.

For more than 30 years, an effective vaccine against HIV has eluded scientists, and more than two million people are still newly infected with the virus each year. In a recent study, scientists at The Scripps Research Institute gained a new weapon in that long fight. They identified four antibodies targeting a specific weak spot on HIV that provided key information for the design of a potential HIV vaccine candidate.

“This study [no paper reference in article]is an example of how we can learn from natural infection and translate that information into vaccine development,” said TSRI Research Associate Raiees Andrabi. “This is an important advance in the field of antibody-based HIV vaccine development.”

Dr. Andrabi served as first author of the study, working in the lab of senior author TSRI Professor Dennis R. Burton, who is also scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI.

The findings build on the success of several recent TSRI studies showing that, with prompting, the immune system can develop antibodies to neutralize many strains of HIV. In the new study, the researchers carried out a series of experiments involving virus modifications and protein and antibody engineering. They found that four antibodies targeted a single spot on HIV’s surface called the V2 apex. This was significant because the V2 apex could be recognized by these antibodies on about 90 percent of known HIV strains – and even related strains that infect other species, meaning a vaccine that targets this region could protect against many forms of the virus.

“This region helps stabilize the virus, so it’s an important area to target if you want to neutralize HIV,” said Dr. Andrabi.

Investigating further, the researchers noticed that two of the four antibodies had an unusual feature that could prove important in vaccine design. The immune system usually begins its fight against infection by activating immune B cells that express “germline” forms of antibodies on their surface to bind invading pathogens. Germline antibodies rarely bind viruses very effectively themselves; instead, they are precursors for more developed antibodies, which mutate and hone their response to the invader.

Yet in the new study, two of the antibodies did not need to mutate to bind with the V2 apex; instead, these antibodies used part of their basic germline structure, encoded by non-mutated genes. This means any patient with HIV should, in theory, have the ability to kick-start the right immune response.

To generate that response, it was critical for the scientists to find the right proteins in HIV that the antibodies could recognize and bind to. In the new study, the researchers succeeded in mimicking a structure on HIV called the native HIV coat protein. This enabled them to design proteins that do indeed bind well to the germline antibodies and hopefully start a useful immune response. The next step will be to test the vaccine candidates in animal models.

See the full article here .

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The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.