Immune Response to Cryptosporidiosis in a Birth Cohorot of Children of South Indi

描述（由申请人提供）：这项由马萨诸塞州波士顿塔夫茨-新英格兰医学中心和印度韦洛尔基督教医学院合作进行的研究的总体目标是调查印度南部儿童对天然隐孢子虫感染的免疫反应。隐孢子虫病是发展中国家儿童腹泻的重要原因，也是研究地点寄生虫腹泻的最常见原因。人类对隐孢子虫病保护性免疫的相关性了解甚少，关于对这种寄生虫的免疫是否具有亚型特异性的信息也很少。对特定隐孢子虫抗原的自然获得性免疫知识对于设计预防或控制该寄生虫引起的疾病的策略至关重要。第一个具体目的是研究对重组(r)抗原rgp15、rp27、rgp900以及孢子子裂解物的免疫应答在确定从出生到3岁儿童隐孢子虫感染过程中的作用。我们将确定对这些抗原的免疫反应是否与原发性隐孢子虫病感染的控制有关。然后，我们将确定由初次感染引起的对这些抗原的免疫反应是否与对后续感染的保护有关。第二个特定目的是研究对多态gp40抗原的亚型特异性免疫反应。我们将确定隐孢子虫病的反复发作是否涉及相同或不同的隐孢子虫种类和亚型。然后，我们将确定对亚型特异性gp40的免疫反应是否与原发性感染的控制有关，以及在原发性感染中感染亚型1a的儿童中对rgp40 1a的免疫反应是否与随后的同型或异型感染的保护有关。这项研究具有创新性，因为它将是人类隐孢子虫病亚型特异性免疫反应的第一个前瞻性研究。这很重要，因为没有纵向出生队列研究的数据，这些研究涉及保护性免疫与人类对这种疾病的亚型特异性免疫反应的相关性。这些数据将为合理制定干预措施（例如适当的疫苗）提供基础。公共卫生相关性：波士顿塔夫茨-新英格兰医学中心和韦洛基督教医学院之间的这项合作研究的目标是调查印度南部儿童对隐孢子虫的免疫力。这种寄生虫是该地区最常见的寄生虫腹泻原因，目前尚无疫苗。这项研究的结果将有助于开发针对这种寄生虫的疫苗。

DESCRIPTION (provided by applicant): The overall goal of this collaborative study between Tufts-New England Medical Center, Boston MA and Christian Medical College, Vellore, India is to investigate the immune response to natural Cryptosporidium spp. infections in children in southern India. Cryptosporidiosis is an important cause of diarrhea in children in developing countries and is the commonest cause of parasitic diarrhea at the study site. The correlates of protective immunity to cryptosporidiosis in humans are poorly understood and there is little information on whether immunity to this parasite is subtype-specific. Knowledge of naturally acquired immunity to specific Cryptosporidium spp. antigens is essential to design strategies to prevent or control disease caused by this parasite. The first specific aim is to investigate the role of immune responses to recombinant (r) antigens rgp15, rp27, rgp900 as well as sporozoite lysate in determining the course of Cryptosporidium infections in children from birth to 3 years of age. We will determine whether immune responses to these antigens are associated with control of infection in primary cryptosporidiosis. We will then determine whether immune responses to these antigens resulting from the primary infection are associated with protection from subsequent infection. The second specific aim is to investigate subtype-specific immune responses to the polymorphic gp40 antigen. We will determine whether repeated episodes of cryptosporidiosis involve the same or different species and subtypes of Cryptosporidium. We will then determine whether immune responses to subtype-specific gp40 are associated with control of the primary infection and whether immune responses to rgp40 1a in children infected with subtype 1a in the primary infection are associated with protection from subsequent homotypic or heterotypic infection. This study is innovative because it will be the first prospective study of subtype- specific immune response in cryptosporidiosis in humans. It is significant because there are no data from longitudinal birth cohort studies that address correlates of protective immunity together with subtype-specific immune responses to this disease in humans. These data will provide the basis for the logical development of interventions, such as appropriate vaccines. PUBLIC HEALTH RELEVANCE: The goal of this collaborative study between Tufts-New England Medical Center, Boston MA and Christian Medical College, Vellore, is to investigate immunity to Cryptosporidium in children in southern India. This parasite is the commonest cause of parasitic diarrhea in this area and there is no vaccine available. Results obtained from this study will be useful for development of vaccines against this parasite.