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 in developing countries.
Shigellosis is estimated to infect around 160 million people and kill one million worldwide 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. 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.
In a bid to develop a proper animal model for human bacillary dysentery, scientists at the International Vaccine Institute (IVI) 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 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 24 hours after Shigella infection. Significant damage and destruction 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 possessing high levels of mucosal IgA antibodies showed milder symptoms of dysentery than did those that received a placebo alone after Shigella infection, demonstrating the utility of the shigellosis model, the scientists noted.
“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 lab at the IVI who led 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, appears in the Feb. 15 issue of the Journal of Immunology.