Team Wins $77 Million to Develop AIDS Vaccine Center

By Mika Ono

The Scripps Research Institute has been awarded a grant expected to total more than $77 million from the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). The new seven-year project will focus on developing a vaccine against HIV and the disease it causes, AIDS.

“With 33 million infected individuals worldwide, an HIV vaccine is urgently needed to slow and eventually eliminate new infections,” said Scripps Research President and CEO Michael A. Marletta. “I am excited that the institute’s proven track record in fundamental discoveries applicable to vaccine development will be brought to bear on this most important and compelling problem.”

“Although AIDS drugs have extended the lives of many, an effective HIV vaccine could truly eliminate the threat of HIV in both developing and developed countries,” said Scripps Research Professor Dennis Burton, a prominent HIV expert who will lead the new center. “We look forward to making significant progress toward this goal in the coming years.”

The Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID) will conduct multidisciplinary research into immune responses that prevent infection or control the virus in infected individuals. The team will also generate vaccine components to induce such immune responses and provide broad protection against HIV infection.

The CHAVI-ID award to Scripps Research was one of two in the nation. The other went to Duke University in Durham, NC.

A Scientific Challenge

HIV (human immunodeficiency virus) causes AIDS (acquired immune deficiency syndrome) by binding to, entering, and ultimately leading to the death of T helper cells, which are immune cells that are necessary to fight off infections by common bacteria and other pathogens. As HIV depletes the body of T helper cells, the immune system fails and common pathogens can become potentially lethal.

An effective HIV vaccine would induce antibodies (specialized immune system molecules) against the virus prior to exposure to the virus. These antibodies would circulate through the blood, and track down and bind to the virus, preventing infection of T helper or other cells.

Most of the antibodies that the body produces to fight HIV, however, are ineffective. The surface of the virus is cloaked with sugar molecules that prevent antibodies from slipping in and blocking the proteins the virus uses to latch onto a cell and infect it. To make matters more complicated, HIV is constantly mutating, so there are multiple HIV strains that antibodies elicited by any vaccine must be able to sense and destroy.

Nonetheless, rare, “broadly neutralizing antibodies” against HIV do exist, as scientists at Scripps Research and other institutions have shown.

Harnessing the Immune System

Under the auspices of the new grant, the team based at Scripps Research will conduct research on antibodies and B cells, the cells that make antibodies. This work will guide the development of immunogens—substances that evoke an immune response—capable of eliciting protective antibodies to HIV.

Additionally, the scientists will focus on studying CD4+ T cells in an attempt to harness these cells’ direct antiviral activity, as well as their ability to help B cells produce antibodies.

“We will work toward an HIV vaccine based on a deep understanding of the critical attributes of immune responses that provide protection against AIDS viruses, through these two focused and highly integrated efforts,” said Burton, who, in addition to his position at Scripps Research, is scientific director of the International AIDS Vaccine Initiative’s (IAVI) Neutralizing Antibody Center, based on the Scripps Research campus in La Jolla, CA, and program leader at The Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University.

The initial award (grant number UM1AI100663-01) provides $11.1 million for the first year of the Scripps Research-based center.

In addition to Burton as director, the center’s scientific leaders include: Rafi Ahmed of Emory University; Michel Nussenzweig of The Rockefeller University/Howard Hughes Medical Institute; Bruce Walker of The Ragon Institute; and Ian Wilson of Scripps Research. Other scientists working on the project include Dan Barouch of Beth Israel Medical Center; Shane Crotty of La Jolla Institute for Allergy & Immunology; Adam Godzik of Sanford-Burnham Medical Research Institute; Daniel Kaufmann of the Ragon Institute; Julie McElrath of Fred Hutchinson Cancer Research Center; Bali Pulendran and Guido Silvestri of Emory University; and Chris Scanlan of Oxford University; as well as Sal Butera, William Schief, and Richard Wyatt of Scripps Research.

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