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‘Designer Bacteria’ May Lead to Better Vaccines

E. coli adjuvants could transform vaccine design (Jan. 15)

Researchers at the University of Texas at Austin have developed a menu of 61 new strains of genetically engineered bacteria that may improve the efficacy of vaccines for diseases such as influenza, pertussis, cholera, and human papillomavirus (HPV) infection.

The strains of Escherichia coli — described in a paper published in the Proceedings of the National Academy of Sciences — are part of a new class of biological adjuvants that could transform vaccine design, the researchers say.

Adjuvants — substances added to vaccines to boost the human immune response — were discovered in the early years of commercial vaccine production, when it was noticed that batches of vaccine that were accidentally contaminated often seemed to be more effective than those that were pure.

Researchers eventually realized that they could produce a one-two punch by intentionally adding their own adjuvant to the mix. The main ingredient of the vaccine — a killed or inactivated version of the bacteria or virus that the vaccine is meant to protect against — did what it was supposed to do. It “taught” the body’s immune system to recognize it and to produce antibodies in response to it.

An adjuvant amplifies that response by triggering a more general alarm, which puts more agents of the immune system into circulation in the bloodstream, where they can learn to recognize the key antigen. The result is an immune system more heavily armed to fight the virus or bacteria when it encounters it in the future.

For about 70 years, the adjuvant of choice in nearly every vaccine worldwide was an aluminum salt. Then, in 2009, the FDA approved a vaccine for HPV infection that included a new kind of adjuvant — a modified version of an endotoxin molecule. These molecules 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 quickly to them.

“In some of its forms, an endotoxin can kill you,” said Dr. M. Stephen Trent, associate professor of biology. “But the adjuvant, which is called MPL [3-O-desacyl-4’-monophosphoryl lipid A], is a very small, carefully modified piece of it, so it’s able to trigger the immune response without overdoing it.”

Trent and his colleagues have expanded on that basic premise. Rather than work with an inert piece of endotoxin, they’ve engineered E. coli bacteria to express the endotoxin in many configurations on the cell surface. One form might work better with cholera vaccine, another with pertussis vaccine, and another with a future human immunodeficiency virus (HIV) vaccine.

Trent said that an additional advantage of their system is that the E. coli bacteria can be engineered to express key viral and bacterial antigens along with the endotoxin. A single cell could deliver both parts of the one-two punch, or even a one-two-three punch, if antigens from multiple diseases were expressed in a single E. coli.

“It makes possible a vaccine that provides protection from multiple pathogens at the same time,” Trent said.

Source: University of Texas at Austin; January 15, 2013.

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