Neonatal immunity against C. trachomatis infections

描述（由申请人提供）：在所有性传播细菌性疾病中，沙眼衣原体感染是世界上所有国家最常见的疾病。大多数孕妇感染C.沙眼病毒在新生儿出生时传播感染。新生儿衣原体感染包括包涵体结膜炎和肺炎。在美国，新生儿感染率为每1 000名活产8.2人。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，包括药物治疗方案的依从性、持续感染的发展、抗生素耐药菌株的出现和药物过敏。此外，在人群水平上，抗生素治疗与再感染的易感性增强有关。因此，开发治疗性疫苗或治疗新生儿感染可能是解决这些问题的有效方法。由于目前缺乏合适的动物模型，对C。新生儿期的沙眼感染有限。本实验室最近建立了新生小鼠C.沙眼感染使用C.沙眼小鼠肺炎生物型（MoPn）。在该模型中，在48小时龄时鼻内接种先前感染MoPn的母鼠所生的新生幼崽。然后在接种后的不同天数对幼仔实施安乐死，以监测其肺中的细菌负荷。本研究的总体目标是鉴定介导C.新生儿沙眼感染。更具体地说，本研究将探讨Th 1免疫在解决C.新生儿期沙眼感染。这项研究的假设是，Th 1介导的免疫需要解决C。新生儿沙眼感染。为了检验该假设，新生幼崽将接受MoPn特异性T细胞或Th 1调节/介导细胞因子，并且鼻内感染将用于评估过继免疫的功效。我们预测Th 1免疫增加的新生儿将清除C。沙眼感染更有效地比非受体新生儿。本研究结果将有助于我们开发一种治疗性的新生儿C.沙眼感染 公共卫生相关性：沙眼衣原体感染在发达国家和不发达国家都是一个主要的健康问题。该提案的目标是为衣原体感染母亲所生的新生儿开发疫苗。用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.