Scientists have developed a way of delivering broadly neutralizing antibodies in mice, and in doing so, have effectively protected them from HIV infection.
Over the past year, researchers at the California Institute of Technology (Caltech), and around the world, have been studying a group of potent antibodies that have the ability to neutralize HIV in the lab, and their hope is that they may learn how to create a vaccine that makes antibodies with similar properties.
Now, biologists at Caltech led by Nobel Laureate David Baltimore, president emeritus and Robert Andrews Millikan Professor of Biology, have taken one step closer to that goal and have developed a new approach to HUIV prevention, called Vectored ImmunoProphylaxis or VIP.
Traditional efforts to develop a vaccine against HIV have been centered on designing substances that provoke an effective immune response, either in the form of antibodies to block infection or T cells that attack infected cells. With VIP, protective antibodies are being provided up front.
“VIP has a similar effect to a vaccine, but without ever calling on the immune system to do any of the work,” Alejandro Balazs, lead author of the study, said.
“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 equation,” he said.
Since mice are not sensitive to HIV, the researchers used specialized mice carrying human immune cells that are able to grow HIV. They utilized an adeno-associated virus (AAV), a small, harmless virus that has been useful in gene-therapy trials, as a carrier to deliver genes that are able to specify antibody production.
The AAV was injected into the leg muscle of mice, and the muscle cells then put broadly neutralizing antibodies into the animals’ circulatory systems.
Researchers found that the treated mice in the study appeared to have 100 percent protection against HIV.
It was also found that after just a single AAV injection, the mice produced high concentrations of these antibodies for the rest of their lives, as shown by intermittent sampling of their blood. Remarkably, these antibodies protected the mice from infection when the researchers exposed them to HIV intravenously.
According to the researchers, the leap from mice to humans is large, and the fact that the approach works in mice does not necessarily mean it will be successful in humans.
Still, the researchers believe that the large amounts of antibodies that the mice were able to produce, coupled with the finding that a relatively small amount of antibody has proved protective in the mice, may translate into human protection against HIV infection.
“We’re not promising that we’ve actually solved the human problem,” he said.
“But the evidence for prevention in these mice is very clear,” Baltimore added.
The study has been published in the journal Nature.