Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre‐clinical assessment of Shigella vaccine formulations. Issue 6 (13th September 2013)

• Record Type: Journal Article
• Authors: Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J.
• Is Part Of: Apmis. Volume 122:Issue 6(2014:Jun.)
• Page Start: 463
• Page End: 475
• Publication Date: 2013-09-13
• Subjects: Pathology -- Periodicals; Microbiology -- Periodicals; Immunology -- Periodicals; 572
• DOI: 10.1111/apm.12168
• Languages: English
• ISSNs: 0903-4641

Abstract

<abstract abstract-type="main" id="apm12168-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood‐ and mucus‐streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre‐clinical evaluation of vaccines candidates. In this study, the minimal dose of <italic>Shigella dysenteriae</italic>1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10<sup>8</sup>, 2 × 10<sup>9</sup> and 2 × 10<sup>10</sup> colony forming unit (CFU)] was determined. In addition, the monkeys were re‐infected. The identified optimal challenge dose was 2 × 10<sup>9</sup> CFU; this dose elicited 60% protection in monkeys when they were re‐challenged with a one log higher dose (2 × 10<sup>10</sup> CFU). The challenge dose, 2 × 10<sup>10</sup> CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re‐challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre‐clinical evaluation of <italic>Shigella</italic> vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re‐challenges with homologous strains.</p> </abstract>