An article in this month’s issue of PNAS indicates that scientists successfully engineered a new tool that may change the way we design vaccines. Brittany Needham and her colleagues at the University of Texas at Austin designed 61 new strains of E. coli bacteria, which can be used to boost the immune system in specific ways.
Vaccines are commonly composed of two components: an antigen and an adjuvant. Each component serves a purpose. The antigen purposefully triggers an immune response, while the adjuvant – discovered by accident around 70 years ago – promotes a more robust immune response, which leads to more long-term immunity.
In the vast majority of vaccines, aluminum salt serves as the adjuvant. However, in 2009, the FDA approved the first endotoxin (endotoxins are toxic substances found inside the cell walls of bacteria, which are released when the cell wall ruptures) adjuvant for mass production in the human papillomavirus vaccine. In large quantities or unaltered forms, endotoxins can kill you, but much like the dead or attenuated viruses currently used in vaccines, these endotoxins are purposefully built and dosed to produce a safe and protective effect. However, designing a specific endotoxin can be laborious and haphazard, so Needham and fellow researchers decided to start designing new endotoxins at their source: bacteria.
By modifying lipids in the bacteria, scientists created E. coli that produce various endotoxins on their cellular surface. When used as an adjuvant, the endotoxins amplify the speed and longevity of the immune system’s response to antigens or other immune-provoking components of the vaccine.
What makes the new E. coli bacteria particularly enticing is their adaptability. Right now, it seems like designer endotoxin can solve many therapeutic dilemmas. According to Stephen Trent, one of the authors on the study, the bacteria can be tweaked to improve vaccines for current epidemics and surges in the United States such as the flu and pertussis. Maybe even HIV. In addition, Trent believes we can design the endotoxins with much more precision and purpose than before. Whereas scientists previously may have designed potential vaccines without an exact knowledge of what the immune response would be, the new bacteria will be more tantamount to a set-and-forget miniature baking oven where we can be sure of what will come out after the “ding”. Indeed, the 61 current E. coli manifestations are only the beginning.
As mentioned above, an adjuvant isn’t the only part of a vaccine. There is also the antigen, or protein component that directly causes an immune response. However, Trent feels the new bacteria could be designed to include bacterial and viral antigens as well, effectively making the new E. coli a one-stop vaccine shop. There is no reason, Trent points out, why the bacteria couldn’t be designed to exhibit the antigens of several pathogens, yielding a single vaccine for multiple diseases. At this point, he is optimistic.
The next step will be clinical trials and FDA approval. Trent is confident that the bacteria will prove fruitful should a company decide to invest in the long process of clinical trials and testing pursuant of FDA standards. In the meantime, Trent and Needham will start research on new E. coli strains to test whether the new endotoxins are as promising as they hope.
