HIV Vaccine Nears Human Trials

A long awaited HIV vaccine has surpassed another hurdle on the way to human testing. The San Diego Union-Tribune has reported on new studies which demonstrate that the immune system could be "primed" in anticipation of attacking the HIV virus.

In a multi-pronged approach, three studies demonstrate various components of a proposed sequential immunization process. Pulling all those elements into a workable human vaccine is the next step, and the studies show researchers are closer than ever to reaching that goal.

Scientists from The Scripps Research Institute, International AIDS Vaccine Initiative, and The Rockefeller University have mapped out each step and demonstrated their efficacy in animal models.

The results of the studies were released simulaneously, two in the journal Science and the third in the journal Cell.

One of the Science studies shows it is possible to to trigger the production of antibodies with an engineered molecule mimicing a vulnerability on the HIV virus. The production of these antibodies prime the immune system so it is ready to build more effective antibodies in response to exposure to substances that mimic other aspects of HIV.

The study in Cell demonstrated how another engineered molecule could be introduced, causing the production of even more mature antibodies. This engineered molecule was also the subject of the second Science study, which showed that it was effective as an HIV vaccination in rabbits. 

"The results are pretty spectacular," said Dennis Burton in a press release. Burton is chair of the Scripps' Department of Immunology and Microbial Science and scientific director of the National Institutes of Health Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery .

"It worked much better than we expected," David Nemazee, another NIH researcher, told the San Diego Union-Tribune. “So we’re quite positive now about trying something more complicated, like a human.”

In fact, the results are strong enough to warrant human testing, but that doesn't mean it will happen overnight. 

“Whenever you get a result that is encouraging, the next step is to see if we can duplicate that in a very gradual, safe, gingerly way in humans in a Phase 1 trial,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, who has been researching HIV for decades. 

The scientists envision a future human vaccine as a series of vaccinations given over the course of a few weeks or months. Each vaccination would build on the other, preparing the immune system so it can make antibodies that neutralize an entire spectrum of HIV strains. Then, when HIV does enter the body, the immune system is able to fight off the infection.

This vaccine strategy is based on how the immune system naturally responds to HIV exposure without the help of a vaccine. Currently most HIV-positive patients end up with compromised immune systems if they aren't on antiretroviral medications. Although the body's immune system tries to fight back, HIV has two advantages:  it mutates frequently and reservoirs of the virus can lurk unseen in a patient's lymphatic system, only to become viable again years later.  

Recognizing that there are a handful of people who test positive for the HIV-virus but don't experienced any problems with their immune systems, the researchers felt in those circumstances the patients' systems had produced broadly neutralizing antibodies that fought off the infection. 

Dr. Richard Pollard of the University of California at Davis has said that in less than one percent of those who are HIV-positive, the immune system seems capable of controlling the virus and preventing it from damaging cells. There are only 500 of those people, officially known “elite controllers,” in the world (including this Sacramento womanPlus wrote about recently).

The researchers at TSRI set out to mimic the antibodies produced by elite controllers and use them to protect HIV-negative individuals from contracting the disease. The first step is to stimulate the immune system to make more of a subtype of B cells that can produce these broadly neutralizing antibodies. That primes the immune system but it still has hurdles to fight off HIV.

One of the researchers compared the HIV virus to the Death Star of Star Wars fame, saying, "The Death Star is covered with stuff that is irrelevant. You could attack it and nothing would happen.” Similarly, the HIV virus is covered in proteins that the immune system focuses on instead of attacking vulnerable regions of HIV. But, by mimicing the receptors HIV uses to invade the cell, the researchers figured out how to trick the virus into thinking these antibodies are the kind of immune cells the virus attacks. 

"So they bind to the same place in HIV that HIV uses to contact our cells and infect them," William Schief told Union-Tribune.

Over the decades of studying the HIV virus, researchers have repeatedly learned that the virus is more complex than they'd previously imagined, and this is why an HIV virus has taken so long to develop.  In contrast, there is already an Ebola vaccine being tested in humans.

“[HIV]'s much more complicated than with plain ol’ vaccinology, where you walk away with your flu shot and you’re done,” Fauci said. “Once you get the right antigen, you’re good to go with those others. That’s the reason we’re testing an Ebola vaccine right now. [Ebola is] a pretty uncomplicated vaccine.”