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Infectious disease

Gilead, Gritstone form $785 million pact to develop an HIV vaccine

The goal is an immune-boosting therapy that helps people with HIV clear the virus

by Megha Satyanarayana
February 3, 2021 | A version of this story appeared in Volume 99, Issue 5

 

An image of HIV particles budding from an infected cell.
Credit: Science Source
HIV particles budding from an infected cell (magnification is 72,000x). Gilead and Gritstone are collaborating on a therapeutic vaccine to stop the virus.

Gilead Sciences is turning to cancer vaccine technology in its search for new treatments for HIV. The drug company will pay $60 million up front and up to $785 million overall to use Gritstone Oncology’s cancer vaccine platform to develop therapeutic vaccines for HIV. The vaccines would not prevent HIV infection but rather spur the immune system to kill off infected cells.

A therapeutic vaccine could be an important part of what’s known as the kick-and-kill strategy for curing HIV, says Diana Brainard, head of Gilead’s viral therapeutics group. In kick and kill, one therapeutic stimulates infected but resting cells to start producing HIV particles again, and another ramps up the immune system to kill those cells. The vaccine is part of the kill phase.

“It’s a bold strategy—nobody knows how to do this,” Brainard says. “What it does, it gives the body new immune responses, and we get to choose what those responses will be to more effectively control the virus.”

The idea of a therapeutic vaccine for HIV isn’t new, says Jerome Kim, director general of the International Vaccine Institute and a former head of the US Military HIV Research Program, where he was involved in numerous vaccine trials. HIV vaccines, whether therapeutic or preventative, have been tough nuts to crack, in part because the virus hides inside cells, and even within the same person, Kim says, the virus changes it genetic sequence. That makes developing the right immune-stimulating therapy a challenge.

In cancer vaccines, the general idea is that clinicians treat someone with bits of tumor protein that amp up the immune system, which then sends cells out to seek and destroy tumor cells that also display those bits of protein. Gritstone has cancer vaccines in clinical trials, and some of its validation data suggest that the technology could readily be turned toward an HIV vaccine, says Gritstone’s Chief Scientific Officer, Karin Jooss.

Gritstone’s technology has two parts, Jooss explains. One part uses artificial intelligence to figure out neoepitopes—the bits of protein that end up on the surface of a tumor cell, in the case of cancer, or on the surface of an infected T cell, in the case of HIV. Neoepitopes are often the flags that immune cells look for as a signal to kill. The other part packages self-amplifying RNA, which contains both the genetic sequence of the neoepitope and the genetic instructions that allow the RNA to be made abundantly, into two delivery systems that spur the immune system: an adenovirus for the initial vaccine and nanoparticles for the booster shots.

Jooss says Gritstone scientists decided this process will work for HIV because, while validating the company’s cancer vaccines, they had to determine whether their delivery systems would stimulate a robust immune response. To do this, the scientists turned to something completely unrelated to the cancers they were targeting: monkeys who were infected with the HIV-related simian immunodeficiency virus (SIV). Not only did the delivery systems cause a strong immune response, but that response was chock full of cells that could recognize SIV later, Jooss says.

“Even one and half years after vaccination, we find very strong memory T cells in these monkeys,” she says.

Tumor genomes are immense, and HIV’s genome is minuscule in comparison. Scientists have been studying which bits of viral protein might lead to the strongest immune response, but Jooss says Gritstone and Gilead have not yet determined which of those neoepitopes to pursue.

Kim is curious whether Gritstone’s approach will work with HIV. Experimental treatments can work well in animal models, including primates with SIV, and then not work in humans, he notes. HIV’s genetic sequence varies, even within the same person, so a therapeutic vaccine approach may kill off a good percentage of virus in a person’s body while leaving some behind.

But given Gilead’s immune-modulating portfolio, which includes the slate of broadly neutralizing antibodies the firm recently acquired from Rockefeller University, it makes sense to continue to work on therapeutic vaccines as part of a larger treatment armament, Kim says.

“We don’t have the right vaccines, or they aren’t powerful enough, and they’re not generating the right immune responses. So, again, there’s still some work here,” he says, summarizing the effort. “A vaccine, a good vaccine … could induce, if not the elimination of the virus, at least suppression so people can go off therapy.”

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