Comparison of rhesus and cynomolgus macaques in a Streptococcus pyogenes infection model for vaccine evaluation
Comparison of rhesus and cynomolgus macaques in a Streptococcus pyogenes infection model for vaccine evaluation
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DOI：
10.1016/j.micpath.2010.10.004
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Heinrichs, Jon H.
中科院分区：
文献类型：
--
作者：
Skinner, Julie M.;Caro-Aguilar, Ivette C.;Heinrichs, Jon H.
预测人类疾病的动物模型通常难以建立和复制。在主要是人类病原体的A群链球菌（GAS）细菌的情况下，动物模型的毒力评估是有问题的。我们比较了猴子定植和两种猕猴感染的咽炎模型，以确定候选疫苗评估的最佳模型。恒河猴和食蟹猴鼻内感染了一种链霉素耐药（Str(r)） GAS菌株。研究人员监测了猴子的体重和体温变化，收集了喉咙拭子和血清，并在整个研究过程中记录了临床观察结果。这两个物种都表现出GAS在口咽的定植，恒河猴在攻击后28天表现出更持久的定植。兽医观察显示，感染气体的恒河猴和食蟹猴之间没有显著差异。在整个研究过程中，模拟感染的猴子没有表现出临床症状或气体定植。ELISA结果显示恒河猴和食蟹猴均出现抗链溶血素o抗体滴度，食蟹猴抗体滴度较高。在免疫荧光试验中，受感染猴子的血清产生调理噬细胞杀伤并与细菌结合。恒河猴和食蟹猴均可用于该GAS M3菌株的定植研究，但仅观察到轻度咽炎和扁桃体炎的临床症状。(C) 2010年Elsevier Ltd.出版。
Animal models predictive of human disease are generally difficult to establish and reproduce. In the case of the Group A Streptococcus (GAS) bacterium, which is predominantly a human pathogen, virulence assessment in animal models is problematic. We compared a monkey colonization and pharyngitis model of infection in two macaque species to determine the optimal model for vaccine candidate evaluation. Rhesus and cynomolgus macaques were intranasally infected with a streptomycin resistant (Str(r)) GAS strain. Monkeys were monitored for body weight and temperature changes, throat swabs and sera were collected, and clinical observations were noted throughout the study. Both species exhibited oropharyngeal colonization by GAS, with rhesus macaques demonstrating a more sustained colonization through day 28 post-challenge. Veterinary observations revealed no significant differences between GAS-infected rhesus and cynomolgus macaques. Mock-infected monkeys did not exhibit clinical symptoms or GAS colonization throughout the study. ELISA results demonstrated that both rhesus and cynomolgus macaques developed anti-streptolysin-O antibody titers, with cynomolgus generating higher titers. Sera from infected monkeys produced opsonophagocytic killing and bound to the bacterium in an immunofluorescence assay. Both rhesus and cynomolgus macaques can be used for colonization studies with this GAS M3 strain, yet only mild clinical signs of pharyngitis and tonsillitis were observed. (C) 2010 Published by Elsevier Ltd.