Engineering Vaccines to Target Multiple Pathogens

Pathogens that come in multiple strains, such as the influenza virus or HIV, are the bane of vaccine developers: A vaccine effective against one strain may provide little immunity to others. Now, a team of Australian researchers has devised a scheme that could eventually lead to a one-shot vaccine that would protect against different strains of the same pathogen or--perhaps--different pathogens entirely.

The new work, which will be published tomorrow in the Journal of the American Chemical Society, focuses on a notion that has long been a lure for vaccine developers: constructing a synthetic vaccine from fragments of a pathogen's proteins. Unlike conventional vaccines made from live attenuated pathogens or killed organisms, such a vaccine would carry no risk of infection. But when researchers have tried injecting patients with peptide fragments, either on their own or attached to a polymer "backbone," they typically haven't generated enough of an immune response to provide protection.

Immunologist and chemist David Jackson and his colleagues at the University of Melbourne in Australia have hit on a new way to challenge the immune system with hundreds of peptides at once, a strategy which they hope will boost the immune response. The researchers started by using conventional techniques to synthesize groups of peptides containing nine different configurations, or epitopes, recognized by the immune system. They then linked a chemical group called acryloyl chloride to the end of each of the synthesized peptides and, with the help of a highly reactive compound and a catalyst, coaxed the acryloyl groups to join together. The result, says Jackson, is a polymer chain that "looks like a necklace with the peptides hanging off of it like pendants."

These concoctions sparked an immune response in mice that was up to 30 times higher than the response generated by the peptides by themselves. Next, the researchers plan to add peptides that mirror epitopes from organisms such as the malaria parasite and streptococci to their synthetic vaccines and test them in animals to see if they protect against the natural organisms.

Although the protective value of the new synthetic vaccines is still unknown, the synthesis scheme is already drawing raves. "This sounds like a very nice approach," says synthetic vaccine expert Jindrich Kopecek of the University of Utah in Salt Lake City. One big advantage is that researchers could easily change the peptides they link together. Ultimately, that ability could allow researchers to create synthetic vaccines with peptides representing multiple epitopes of single organisms, related epitopes from different strains of the same organism such as HIV, or epitopes from an array of different pathogens.