EpidemicsScientists develop a new way to prevent the spread of deadly diseases

Published 19 September 2014

For decades, researchers have tried to develop broadly effective vaccines to prevent the spread of illnesses such as HIV, malaria, and tuberculosis. While limited progress has been made along these lines, there are still no licensed vaccinations available that can protect most people from these devastating diseases. So what are immunologists to do when vaccines just aren’t working? Whereas vaccines introduce substances such as antigens into the body hoping to illicit an appropriate immune response — the generation of either antibodies that might block an infection or T cells capable of attacking infected cells — Caltech scientists have approached the problem in a different way: Why not provide the body with step-by-step instructions for producing specific antibodies that have been shown to neutralize a particular disease?

For decades, researchers have tried to develop broadly effective vaccines to prevent the spread of illnesses such as HIV, malaria, and tuberculosis. While limited progress has been made along these lines, there are still no licensed vaccinations available that can protect most people from these devastating diseases.

So what are immunologists to do when vaccines just aren’t working?

At Caltech, Nobel Laureate David Baltimore and his colleagues have approached the problem in a different way. Whereas vaccines introduce substances such as antigens into the body hoping to illicit an appropriate immune response — the generation of either antibodies that might block an infection or T cells capable of attacking infected cells — the Caltech team thought: Why not provide the body with step-by-step instructions for producing specific antibodies that have been shown to neutralize a particular disease?

A CalTech release reports that the method they developed — originally to trigger an immune response to HIV — is called vectored immunoprophylaxis, or VIP. The technique was so successful that it has since been applied to a number of other infectious diseases, including influenza, malaria, and hepatitis C.

It is enormously gratifying to us that this technique can have potentially widespread use for the most difficult diseases that are faced particularly by the less developed world,” says Baltimore, president emeritus and the Robert Andrews Millikan Professor of Biology at Caltech.

VIP relies on the prior identification of one or more antibodies that are able to prevent infection in laboratory tests by a wide range of isolated samples of a particular pathogen.

Once that has been done, researchers can incorporate the genes that encode those antibodies into an adeno-associated virus (AAV), a small, harmless virus that has been useful in gene-therapy trials. When the AAV is injected into muscle tissue, the genes instruct the muscle tissue to generate the specified antibodies, which can then enter the circulation and protect against infection.

In 2011, the Baltimore group reported in Nature that they had used the technique to deliver antibodies that effectively protected mice from HIV infection. Alejandro Balazs was lead author on that paper and was a postdoctoral scholar in the Baltimore lab at the time.