Neonatal immunity against C. trachomatis infections

描述(申请人提供)：在所有的性传播细菌疾病中，沙眼衣原体感染是世界上所有国家最常见的疾病。大多数感染沙眼衣原体的孕妇在出生时会将感染传播给新生儿。新生儿衣原体感染包括包涵性结膜炎和肺炎。在美国，新生儿感染率为每1000名活产儿中有8.2人感染。这些感染与高发病率和经济损失有关，但如果及时诊断，可以用抗生素治疗。然而，抗生素的使用产生了几个潜在的问题，包括遵守药物方案、发展持续感染、出现耐药菌株和药物过敏。此外，抗生素治疗与在人群水平上增加再次感染的敏感性有关。因此，开发治疗性疫苗或治疗新生儿感染可能是对抗这些问题的有效途径。由于我们目前缺乏合适的动物模型，对新生儿期沙眼衣原体感染的了解有限。最近，我们实验室利用沙眼衣原体小鼠肺炎生物型(MoPn)建立了沙眼衣原体感染的新生小鼠模型。在这个模型中，出生于之前感染过MoPn的水坝的新生幼崽在48小时龄时被鼻腔接种。然后在接种后的不同时间对幼崽实施安乐死，以监测它们肺部的细菌负荷。这项研究的总体目标是确定Th1免疫成分在调节新生儿沙眼衣原体感染中的作用。更具体地说，这项研究将调查Th1免疫在解决新生儿时期沙眼衣原体感染方面的作用。这项研究的假设是，需要Th1介导的免疫来解决新生儿生活中的沙眼衣原体感染。为了验证这一假设，新生幼崽将接受MoPn特异性T细胞或Th1调节/介导性细胞因子，鼻腔感染将用于评估过继免疫的效果。我们预测，增加Th1免疫的新生儿将比未接受Th1免疫的新生儿更有效地清除沙眼衣原体感染。这项研究的结果将有助于我们开发针对沙眼衣原体感染的治疗性新生儿疫苗。公共卫生相关性：沙眼衣原体感染在发达国家和欠发达国家都是一个主要的健康问题。这项提案的目标是为衣原体感染母亲所生的新生儿开发一种疫苗。通过疫苗降低这些感染的发病率和流行率将对全世界的健康产生重大影响。

DESCRIPTION (provided by applicant): Of all sexually transmitted bacterial diseases, Chlamydia trachomatis infections are the most common ones in all nations of the world. Most pregnant women infected with C. trachomatis transmit infections to their neonates at birth. Neonatal chlamydial infections include inclusion conjunctivitis and pneumonia. In the U.S., the rate of neonatal infection is 8.2 per 1,000 live births. These infections are associated with a high incidence of morbidity and economic loss, but if diagnosed in time, can be treated with antibiotics. However, the use of antibiotics creates several potential problems, including compliance with medicine regimens, development of persistent infections, emergence of antibiotic- resistant strains, and drug allergies. In addition, antibiotic treatment has been associated with enhanced susceptibility to reinfection at the population level. Therefore, development of a therapeutic vaccine or treatment for neonatal infections may be an effective way to counteract these problems. Because we currently lack an appropriate animal model, knowledge of C. trachomatis infections during the neonatal period is limited. Recently, our laboratory developed a neonatal mouse model of the C. trachomatis infection using the C. trachomatis mouse pneumonitis biovar (MoPn). In this model, newborn pups born to previously MoPn-infected dams are inoculated intranasally at 48 hours of age. Pups then are euthanized at various days post-inoculation to monitor bacterial burden in their lungs. This study's overall aim is to identify a Th1 immune component in mediating a C. trachomatis infection in neonates. More specifically, the research will investigate the role of Th1 immunity in resolving C. trachomatis infections during the neonatal period. This study's hypothesis is that a Th1- mediated immunity is needed to resolve a C. trachomatis infection in neonatal life. To test the hypothesis, newborn pups will receive MoPn-specific T-cells, or Th1-modulating/mediating cytokines, and an intranasal infection will be used to evaluate the efficacy of the adoptive immunity. We predict that neonates with added Th1 immunity will clear C. trachomatis infections more effectively than the non-recipient neonates. The study's result will help us to develop a therapeutic neonatal vaccine against C. trachomatis infections. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis infections are a major health problem in both developed and underdeveloped countries. The goal of this proposal is to develop a vaccine for the newborn babies who are born from Chlamydia infected mothers. Decreasing the incidence and prevalence of these infections with a vaccine will have a major health impact worldwide.