Biologists one step closer to neutralizing HIV

A new vaccination approach out of CalTech focuses on providing protective antibodies upfront, rather than designing substances that will provoke an effective immune response.

Researchers around the world have been studying a group of recently-identified antibodies capable of neutralizing most strains of HIV, with the hopes of developing a vaccine that produces antibodies with these same properties.

This illustration shows the crystal structure of the adeno-associated virus used to deliver antibodies against HIV. Alejandro Balazs/California Institute of Technology

Now, biologists out of the California Institute of Technology--led by Nobel Laureate David Baltimore--are one step closer to a vaccine with their new method of delivering these antibodies to lab mice, thereby protecting them from HIV.

Their approach, called Vectored ImmunoProphylaxis (VIP) and outlined in today's online issue of Nature, turns the traditional vaccination method on its head.

For the most part, researchers have focused on designing substances that activate the immune system to do one of two things: block infection via antibodies, or attack infected cells via T cells. But the VIP approach provides protective antibodies from the start.

"Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it," says Alejandro Balazs, lead author of the study and a postdoctoral scholar in Baltimore's lab, in a news release. "We've taken that whole part out of the equation...without ever calling on the immune system to do any of the work."

In fact, after a single dose of the harmless adeno-associated virus into the leg muscles of mice, those muscle cells directed broadly neutralizing antibodies into the circulatory systems, and the mice produced high concentrations of these antibodies for the rest of their lives. When researchers exposed mice to HIV intravenously, those antibodies protected them from infection.

Unfortunately, there is a significant leap from mice to humans. For one, mice are not sensitive to HIV, so the researchers used mice that had human immune cells capable of growing HIV.

But the team says that two findings--the animal's ability to produce large amounts of antibodies, and the effectiveness of protection with just a small amount of those antibodies--shows promise, and could translate into human protection as well.

What's more, when the team exposed the mice to a virus dose of one nanogram, which was sufficiently high to infect most mice and yet didn't, they continued to increase exposure levels until they hit 125 nanograms--100 times more than the amount needed to infect 7 out of 8 mice. And still, the mice were protected.

"We expected that at some dose, the antibodies would fail to protect the mice, but it never did," Balazs says. "All of the exposures in this work were significantly larger than a human being would be likely to encounter."

Next step: figure out how to test the VIP method in human clinical trials. Initially, the researchers will simply investigate whether the adeno-associated virus is able to program the muscles of humans to produce enough antibodies to be protective against HIV.

 

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