Dr. Mi-Na Kweon (back row, extreme left) and her lab scientists

IVI scientists have developed a new laboratory animal model for shigellosis with guinea pigs in a study that could speed up the development of a vaccine against Shigella dysentery, a major cause of diarrheal deaths amongst children in developing countries.

Shigellosis is estimated to infect around 160 million people and kill one million world-wide every year. But the development of a vaccine against shigellosis, a major form of enteric infection caused by the bacteria, Shigella spp., which often causes bloody diarrhea, has been elusive. Read a related story. This is in part because no suitable animal models exist for the pathogen, which primarily affects humans, making it difficult to evaluate the protective efficacy of vaccine candidates against the disease.     

     
Large intestine                               Large intestine of 
           of normal guinea pig                guinea pig infected with Shigella

 

In an effort to develop a proper animal model for human bacillary dysentery, IVI scientists introduced into guinea pigs various Shigella strains, including virulent S. flexneri 2a or S. flexneri 5a strains, via the intrarectal (IR) route. The scientists found that all guinea pigs that were administered these Shigella strains came down with bloody diarrhea, presumably resulting from acute rectocolitis.

The animals lost about 20% of their body weight within 24 hours after being infected with Shigella. Significant damage of mucosal and submucosal layers, and thickened intestinal wall, among other signs of inflammation, were also observed in the colon.

Most importantly, guinea pigs vaccinated with an attenuated S. flexneri 2a SC602 strain eliciting high levels of mucosal IgA antibodies showed milder symptoms of dysentery than did those that received a placebo alone after Shigella infection. IVI scientists note that this demonstrates the utility of the animal model for shigellosis.

“In the guinea pig, administration of Shigella by the IR route induces acute inflammation. The reactions and associated clinical symptoms virtually mimicked the acute phase of dysentery in humans. This constitutes a unique animal model for assessing the protective efficacy of Shigella vaccine candidates, which could advance the development of a safe and effective vaccine against shigellosis.” said Dr. Mi-Na Kweon, head of the mucosal immunology laboratory at the IVI and leader of the study.

The study, conducted jointly by IVI scientists, Dr. Philippe Sansonetti of the Pasteur Institute of France and Prof. Chihiro Sasakawa of the University of Tokyo, appeared in the Feb. 15, 2007 issue of The Journal of Immunology. Read the article.