Details

Autor(en) / Beteiligte

• Islam, Dilara
• Ruamsap, Nattaya
• Khantapura, Patchariya
• Aksomboon, Ajchara
• Srijan, Apichai
• Wongstitwilairoong, Boonchai
• Bodhidatta, Ladaporn
• Gettayacamin, Montip
• Venkatesan, Malabi M
• Mason, Carl J.

Titel

Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations

Ist Teil von

• APMIS : acta pathologica, microbiologica et immunologica Scandinavica, 2014-06, Vol.122 (6), p.463-475

Ort / Verlag

Denmark: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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 Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 108, 2 × 109 and 2 × 1010 colony forming unit (CFU)] was determined. In addition, the monkeys were re‐infected. The identified optimal challenge dose was 2 × 109 CFU; this dose elicited 60% protection in monkeys when they were re‐challenged with a one log higher dose (2 × 1010 CFU). The challenge dose, 2 × 1010 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 Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re‐challenges with homologous strains.