Huge weak spot found on HIV in Scripps-led study

[Tadeys]

LA JOLLA — A weak spot on the surface of HIV-1, the most prevalent AIDS virus, is far larger than originally thought, according to a study led by scientists at The Scripps Research Institute.

This “supersite of immune vulnerability” may be helpful in developing an AIDS vaccine, said the study published Sunday in Nature Structural & Molecular Biology. Its first author is Leopold Kong and senior author is Ian A. Wilson, both of Scripps.

Much of HIV’s surface mutates rapidly, escaping the body’s immune system and also vaccines. But certain regions of the surface required for infection can’t mutate much. These areas can be targeted by antibodies that neutralize a broad range of HIV strains.

Wilson and colleagues have searched for years for these broadly neutralizing antibodies, which they plan to use as a template for a vaccine. The newly discovered weak region provides a good target for producing even more of the broadly neutralizing antibodies, the paper said.

The paper “tracks a course for the next critical step in vaccine design,” said infectious disease researcher Robert C. Liddington of the Sanford-Burnham Medical Research Institute, who was not involved in the study. Liddington’s research includes broadly neutralizing antibodies, for HIV and influenza, another highly mutable virus.

Producing a so-called universal flu vaccine that protects against the great majority of strains requires some of the same technology needed for an HIV vaccine. Wilson and his colleagues are researching a universal flu vaccine in a partnership with Janssen Pharmaceuticals, a division of Johnson & Johnson.

The vulnerable region occurs on a part of the HIV shell called gp120, used by the virus to attach to cells it infects. Because it performs an essential function, mutations on gp120 are constrained. That appears to make the region an ideal vaccine target.

However, researchers have been unsuccessful in making an effective vaccine from gp120. A 2006 study led by Scripps researcher Dennis Burton found that the vulnerable regions are concealed from the immune system.

The new study found that a portion of gp120 thought to be narrowly accessible to antibodies is much more widely open than previously believed. The region allows antibodies to bind in several different locations and at multiple angles of attachment.

“Now that scientists understand how these special antibodies work, there is real optimism that the next crucial step can be achieved: the synthesis of fragments of gp120 that could act as the major element of a universal vaccine,” Liddington said.

Broadly neutralizing HIV antibodies were originally discovered in some HIV-positive people. But it usually takes two to three years after infection before they’re produced, the paper said. By then, the virus is firmly established.

A vaccine that produces broadly neutralizing antibodies in the uninfected might be able to block HIV before it gets a foothold, the study said. It said the most promising approach could be to put the various antibody-provoking regions, called epitopes, on microscopic scaffolds that prominently display them so the immune system can recognize them.

The study was funded in part under a $77 million, seven-year grant awarded last July by the National Institutes of Health. The grant established the Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, or CHAVI-ID, at Scripps.

Other sources include the International AIDS Vaccine Initiative Neutralizing Antibody, or IAVI, Center, also located at Scripps and the HIV Vaccine Research and Design program.

http://www.utsandiego.com/news/2013/may/26/hiv-neutralizing-gp120/

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