Islam Dilara, Lewis Michael D, Srijan Apichai, Bodhidatta Ladaporn, Aksomboon Ajchara, Gettayacamin Montip, Baqar Shahida, Scott Daniel, Mason Carl J
Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), 315/6 Rajvithi Road, Bangkok 10400, Thailand.
Vaccine. 2006 May 1;24(18):3762-71. doi: 10.1016/j.vaccine.2005.07.023. Epub 2005 Jul 25.
Campylobacter jejuni is a common cause of enteritis worldwide. The mechanisms by which C. jejuni causes disease are unclear. Challenge studies in humans are currently considered unethical due to the possibility of severe complications, such as Guillain-Barré syndrome. Campylobacter infection in non-human primates closely mimics the disease and immune response, seen in humans. In this study, we attempted to determine the minimal dose of a pathogenic C. jejuni 81-176 strain required for clinical signs and symptoms of disease (> or = 80% attack rate) in Macaca mulatta monkeys using an escalating dosage (three doses for three monkey groups: 10(7), 10(9) and 10(11) cfu). Eighty percent of the monkeys challenged with highest dose (10(11) cfu) had mild disease, but the 80% attack rate (moderate diarrhea in 80% of the monkeys) was not achieved. However, 100% of monkeys showed IgA seroconversions (three-fold over pre-challenge titers). The elicited immune response was challenge dose-dependent. Campylobacter antigen specific fecal s-IgA responses were observed in all challenged groups but the response was not dose-dependent. Only IgM antibody secreting cells response was observed against Campylobacter antigens. The elicited immune response in three groups of rhesus monkeys was dose-dependent, indicating this monkey model can be used for pre-clinical evaluation of Campylobacter candidate vaccines, however these adult rhesus monkeys are less prone to Campylobacter infection.
空肠弯曲菌是全球范围内肠炎的常见病因。空肠弯曲菌致病的机制尚不清楚。由于可能出现严重并发症，如吉兰 - 巴雷综合征，目前认为在人体进行激发研究是不道德的。非人灵长类动物的空肠弯曲菌感染与人类所见的疾病和免疫反应密切相似。在本研究中，我们试图使用递增剂量（三个猴组分别给予三剂：10⁷、10⁹和10¹¹ cfu）来确定恒河猴感染致病空肠弯曲菌81 - 176菌株出现疾病临床体征和症状（攻击率≥80%）所需的最小剂量。接受最高剂量（10¹¹ cfu）攻击的猴子中有80%出现轻度疾病，但未达到80%的攻击率（80%的猴子出现中度腹泻）。然而，100%的猴子出现了IgA血清转化（比攻击前滴度高三倍）。引发的免疫反应具有剂量依赖性。在所有攻击组中均观察到空肠弯曲菌抗原特异性粪便分泌型IgA反应，但该反应不具有剂量依赖性。仅观察到针对空肠弯曲菌抗原的IgM抗体分泌细胞反应。三组恒河猴中引发的免疫反应具有剂量依赖性，表明该猴模型可用于空肠弯曲菌候选疫苗的临床前评估，然而这些成年恒河猴较不易感染空肠弯曲菌。
