Better Vaccines Through Designer Bacteria
January 16, 2013

Designer Bacteria Could Possibly Improve Vaccine Effectiveness

Connie K. Ho for — Your Universe Online

Scientists from the University of Texas-Austin (UTA) recently revealed that they have been able to develop 61 new strains of genetically engineered bacteria that could boost the effectiveness of vaccines for diseases such as cholera, HPV, the flu, and pertussis.

The findings on these strains of E. coli were featured in a recent edition of the Proceedings of the National Academy of Sciences. These strains of E. coli are part of a new group of biological “adjuvants” that could help change the way that vaccines are designed. Adjuvants are described as substances that are included with vaccines to increase the human immune response.

"For 70 years the only adjuvants being used were aluminum salts," remarked Stephen Trent, an associate professor of biology in the College of Natural Sciences at UTA, in a prepared statement. "They worked, but we didn't fully understand why, and there were limitations. Then four years ago the first biological adjuvant was approved by the Food and Drug Administration. I think what we're doing is a step forward from that. It's going to allow us to design vaccines in a much more intentional way."

The researchers described how adjuvants were initially found during the earlier years of commercial vaccine production, notably when batches of vaccines were accidentally contaminated but appeared to be more effective than the original pure batches. The scientists eventually discovered that they could create a one-two punch by specifically adding their own adjuvant, or dirt, or the combination. The main element of the vaccine was either a killed or inactivated virus of the bacteria, or a virus that the vaccine could defend against. This way, the body´s immune system could identify it and create antibodies to respond. The adjuvant also elevated the body´s response by initiating a general warning, allowing more agents in the immune system to be circulating in the bloodstream to slowly learn about the key antigen. As a result, the immune system had a strong defense when it needed to combat the virus or bacteria in the future.

"They're called the 'dirty little secret' of immunology," continued Trent in the statement. "If the vials were dirty, they elicited a better immune response."

For the past 70 years, aluminum salt has been used as an adjuvant in almost every vaccine in the world. In 2009, the U.S. Food and Drug Administration (FDA) allowed a new vaccine for the human papillomavirus (HPV). The vaccine had a new type of adjuvant that was a modified format of an endotoxin molecule. In particular, endotoxin is found on the cell surface of a variety of bacteria; humans have changed over millions of years to be able to find and react to them quickly.

"In some of its forms an endotoxin can kill you," explained Trent in the statement. "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."

In the study, the researchers were able to expand on this idea of the endotoxin and engineer the E. coli bacteria to communicate the endotoxin in different versions on the cell surface.

"These 61 E. coli strains each have a different profile on their surface," noted the study´s first author Brittany Needham, a doctoral student working in Trent's lab, in the statement. "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."

As a result, one strain might work with pertussis (whopping cough), while another might work better with a cholera vaccine or future HIV vaccine. The investigators believe that they will be able to tweak the adjuvants in more precise ways as more and more E. coli strains are engineered and then experimented.

"I think we're at the dawn of a new age of vaccine design," commented Trent in the statement. "For a long time vaccinology was really a trial-and-error field. It was a black box. We knew certain things worked. We knew certain vaccines had certain side effects. But we didn't entirely know why. Now that's changing."