Caltech Researchers Try New Approach to Stopping HIV

Successful with Mice

The search for a silver bullet to stop the virus that causes AIDS has led scientists around the world to focus on a group of potent antibodies that can neutralize HIV in a laboratory setting.

Now, scientists at the California Institute of Technology in Pasadena are reporting progress in prompting cells in mice to produce these antibodies.  The Caltech researchers are preparing to move to the next step:  clinical trials in humans.

"We're not promising that we've actually solved the human problem," said Prof. David Baltimore, PhD, the Nobel Laureate who heads the Caltech research team.  "But the evidence for prevention in these mice is very clear."

The key is equipping cells with the genes needed to produce the antibodies.  The Caltech team calls its approach Vectored ImmunoProphylaxis, or VIP.

It is not a vaccine, but has "a similar effect," according to Alejandro Balazs, PhD, lead author of the study published in the journal Nature.

"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.  We've taken that whole part out of the equate," Balazs said.

Normally, mice are not susceptible to HIV.  The Caltech study used specialized mice with human immune cells that were exposed to increasing levels of the virus.

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"We expected that at some dose, the antibodies would fail to protect the mice, but it never occurred--even when we gave mice 100 times more HIV than would be needed to infect 7 out of 8 mice," Balasz said.

The antibodies themselves can be directly injected.  The role of VIP is to enable cells to produce their own antibodies, which can then circulate in great numbers, beyond what had been achieved previously.

"What we managed to do is make a better version of that,  that now could make antibodies to be...prophylacticly useful," Balasz said.

How soon human trials can begin is not yet clear. Caltech is now seeking funding and partners to find out if humans will respond as mice have.

"We have to be prepared for surpises in carrying this work to humans," Baltimore said. "We may have to go back to the  laboratory and solve new problems that we didn't have when we were dealing simply with mice."

VIP for people may still be several years away, but in Dr. Baltimore's view:  "Right now, I think it's the best thing on the horizon."

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