NIH funds testing and development of HIV vaccine

After decades of failure in developing an effective HIV vaccine, the federal government has committed $ 129 million in a new effort led by Scripps Research.

The National Institutes of Health Award was announced Wednesday. It will fund the development and testing of a multi-stage preventive vaccine. The work will be done by the HIV / AIDS Vaccine Development Consortium, or CHAVD, an international collaboration.

Scripps Research scientists in La Jolla will get about half of the funds needed for the seven years of the grant, said Dennis Burton, co-chair of Scripps Research's Department of Immunology and Microbiology and director of CHAVD. The rest goes to 13 other CHAVD groups, including projects at four foreign sites.

The grant from the NIH's National Institute of Allergy and Infectious Diseases implements the knowledge gained through research conducted under a previous seven-year grant, Burton said. A series of vaccines are intended to "train" the immune system to make potent antibodies that neutralize a wide range of HIV strains.

"We have shown that it works on animal models, so we have to integrate that into human reality," Burton said.

This "sequential" vaccination is necessary because the immune system must be motivated before it can effectively fight HIV, said Dr. Anthony Fauci, Director of NIAID.

"You can not just do what you do with the measles vaccine, where you give one shot and two, and then the body immediately produces the right kind of antibodies," Fauci said.

Large neutralizing antibodies have been found in the blood of HIV-positive people. These antibodies usually take years to teach the immune system to make. At this point, HIV is too well established for the body to be eradicated.

The multi-stage vaccine is meant to compress this immune education process in several months, said Burton. It is not known yet how long the process will take or how many steps.

"We will have three, four or maybe five vaccinations," Burton said. "But what will be in the syringe will be different each time, because we bring the antibody response to the desired place, namely these largely neutralizing antibodies."

The full sequence will probably take about nine months, with doses being spaced a few months apart, Burton said. The precise timing will be determined at each stage of the vaccine and the evaluation of the immune response.

Vaccination to launch the response began last September, Burton said. The results of this first step should be available later this year.

The previous grant had resulted in a cascade of discoveries about how the human immune system can defend itself against HIV.

Part of this work aimed to understand how large-scale neutralizing antibodies stop HIV. Other work focused on what needed to be done to generate these antibodies.

Studies have examined whether the sequential vaccination approach works in animals. These studies were conducted by Bill Schief of Scripps Research and other colleagues at Scripps Research and others. The approach was successful.

And a study by Shane Crotty of the La Jolla Institute of Immunology and Scripps Research found that one million "naïve" B cells producing antibodies are capable of becoming of the type producing largely neutralizing antibodies. Crotty is another CHAVD executive in San Diego, alongside Ian Wilson of Scripps Research.

The question was whether enough of these useful B cells could be generated in most immune systems or if this capacity was limited to a few.

The study showed that it was possible for most people, but that these cells required additional exposure to HIV-related immune stimulants to make them mature. The multi-stage vaccine is intended to produce this result.

Fauci said "cautiously optimistic", but it is not certain that this sequential vaccine approach will work.

"I do not know, and it's part of the mystery and excitement of doing this kind of research," said Fauci. "I think we understand the basic concepts."

Fauci also praised the role played by Scripps Research. "They are among the best in the world, so it's one of the reasons I feel cautiously optimistic about our success," Fauci said.

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