For about 70 years the adjuvant of choice, in nearly every vaccine worldwide, was an aluminum salt. Then in 2009, the FDA approved a new vaccine for human papillomavirus (HPV). It included a new kind of adjuvant that's a modified version of an endotoxin molecule.
These molecules, which can be dangerous, appear on the cell surface of a wide range of bacteria. As a result, humans have evolved over millions of years to detect and respond to them quickly. They trigger an immediate red alert.
"In some of its forms an endotoxin can kill you," said Trent. "But the adjuvant, which is called MPL, is a very small, carefully modified piece of it, so it's able to trigger the immune response without overdoing it."
What Trent and his colleagues have done is expand on that basic premise. Rather than just work with an inert piece of endotoxin, they've engineered E. coli bacteria to express the endotoxin in many configurations on the cell surface.
"These 61 E. coli strains each have a different profile on their surface," said Brittany Needham, a doctoral student in Trent's lab and the first author on the paper. "In every case the surface structure of the endotoxin is safe, but it will interact with the immune system in a range of ways. Suddenly we have a huge potential menu of adjuvants to test out with different kinds of vaccines."
One form might work better with cholera vaccine, another with pertussis (whooping cough) and another with a future HIV vaccine. Trent, Needham and their colleagues should be able to fine-tune the adjuvants with increasing precision as more E. coli strains are engineered and tested, and as their understanding of how they interact with the immune system deepens.
"I think we're at the dawn of a new age of vaccine design," said
|Contact: Daniel Oppenheimer|
University of Texas at Austin