New discovery increases efficacy of mouse model in RASV clinical testing

A study recently conducted by researchers of the Arizona State University Biodesign Institute found a way to use the mouse model to more accurately predict the efficacy of recombinant attenuated salmonella vaccines.

The study was led by Karen Brenneman and colleagues Jacquelyn A. Kilbourne, Crystal Willingham, Kenneth Roland and Roy Curtiss III. The use of a mouse model in the study was notable due to the differences in the stomach environment of humans compared to mice.

"Over the years, the mouse model has taught us a lot about how Salmonella interacts with mammalian hosts," Roland said. "However, it turns out that the mouse model fails to provide relevant information on how Salmonella is able to deal with the extremely low pH of the human stomach."

Because RASVs are administered orally, in order to be effective they must be able to withstand the extremely low and hostile stomach environment in humans. Researchers of the study discovered that mice have an average pH of 4.0 on an empty stomach while humans have an average pH of 2.0. After this discovery, the team decided to see if it could lower the pH level of the stomach acid of mice to make the mouse model effective in predicting the efficacy of RASVs.

The researchers were able to decrease the pH level of the mice to 1.5 and improved the vaccine 10-fold to withstand these conditions, making for an effective vaccine that can potentially withstand the hostile conditions of the human stomach.

"Finding a way to temporarily lower the stomach pH of a mouse sets the stage for further research into designing more effective oral vaccines such as RASVs and will provide new insights into how wild-type pathogenic bacteria survive this barrier," Roland said. "Our paper also demonstrates the utility of our previously described, novel acid-resistance systems to increase survival of RASVs in vivo at low pH."