Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected
patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious
problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics
may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of
drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable
animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines.
Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent
human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with
virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated
molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology
of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including
live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands
considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity.
The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal
models currently available, including the newly developed mouse model.