Four Seattle institutions and The Rockefeller University were awarded a seven-year $9.8 million grant from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) toward developing a vaccine designed to elicit broadly neutralizing antibodies against HIV-1.

The consortium will use its Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) grant from NIAID to fund the initial phase of the project, which will include the optimization and preclinical evaluation of two vaccine candidates.

Seattle BioMed will lead the consortium, which will include the University of Washington, Seattle Children’s Hospital, and the Fred Hutchinson Cancer Research Center, as well as Rockefeller University.

“This multidisciplinary collaboration will accelerate the delivery of a novel and effective vaccine to patients,” Alan Aderem, Ph.D., Seattle BioMed’s president, said in a statement.

The new collaboration aims to address two longstanding frustrations researchers have long articulated in describing the challenge of creating an HIV vaccine. One is how to elicit broadly neutralizing antibodies against the virus—a task that requires stimulating B cells that on their surface express B-cell receptors, each cell expressing a specific receptor.

“What we know is the broadly neutralizing antibodies are derived from specific B-cell receptors. The previous vaccines that we have tested, either in animals in the preclinical setting, or even in humans in several clinical trials, those particular vaccines did not actually bind and activate those B cells that expressed those B-cell receptors of interest. The reason is that those vaccines were derived from HIV,” Leonidas Stamatatos, Ph.D., the IPCAVD program principal investigator, told GEN.

“HIV over time has evolved specifically to avoid detection by those B cells. The last thing the virus wants is to activate those B cells that are going to make those antibodies that will be broadly neutralizing,” added Dr. Stamatatos, who is also professor and scientific director, Seattle BioMed. “We found a way to overcome this problem, so we designed vaccines that can now bind the B cells that eventually make those broadly neutralizing antibodies, so we know at least in the lab that we can activate those B cells. Now the big question is, we can do that in the lab, but can we do that in vivo?”

The second frustration: While broadly neutralizing antibodies have shown promise in some people with HIV, researchers are still learning what titers you have to make of the antibodies in order for them to be protective, or how to make them last long enough to be truly effective against the virus.

“Those are key questions which are in the back of our minds, but we’re not really working on it,” Dr. Stamatatos said. “The first thing is to convince ourselves that we can actually make those broadly neutralizing antibodies. And then subsequently, we can think about how long we can keep them, and devise methodologies that will sustain those antibodies for extended periods of time in the body.”

Dr. Stamatatos will lead the project’s initial phase, which includes optimization of the immunogens. Noah Sather, Ph.D., principal scientist at Seattle BioMed; David Rawlings, M.D., Seattle Children’s Research Institute; and Michel Nussenzweig, M.D., Ph. D., Rockefeller University will co-lead the preclinical evaluation of immunogens, while Julie McElrath, M.D., Ph.D., of the Fred Hutchinson Cancer Center and HIV Vaccine Trials Network will oversee the clinical testing of immunogens. 

The project’s second phase will include the production of these vaccines according to cGMP standards and the evaluation of their safety and immunogenicity in a Phase I clinical trial. The consortium looks to start human trials sooner than the scheduled seven years.

“By the end of year five, the aim is to have a product that will go into human volunteers. The latest it will go into humans is years six and seven,” Dr. Stamatatos said.

[The report has been updated from an earlier version to include comments from Leonidas Stamatatos, Ph.D., the IPCAVD program principal investigator and professor and scientific director, Seattle BioMed.]

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