Role of maternal and infant vaccine-induced IgG in protection against pertussis

母婴疫苗诱导的 IgG 在预防百日咳中的作用

• 批准号: 9198485
• 负责人: Marcela F Pasetti
• 金额: $ 19.28万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198485
• 关键词: Acellular Vaccines; Active Biological Transport; Activities of Daily Living; Adult; Affect; Age-Months; Animal Model; Antibodies; Antigens; Blood Circulation; Bordetella pertussis; Bronchoalveolar Lavage; Cells; Child; Childhood; Coughing; Diphtheria; Effectiveness; Epithelial; Epithelium; Experimental Animal Model; Exposure to; Failure; Family; Fc Receptor; Female; Hemagglutinin; Household; Human Milk; Immune; Immune response; Immunity; Immunization; Immunization Schedule; Immunize; Immunoglobulin A; Immunoglobulin G; Incidence; Infant; Infection; Intestines; Lung diseases; Measurement; Measures; Mediating; Milk; Mothers; Mucous Membrane; Mus; Passive Transfer of Immunity; Pertussis; Pertussis Toxin; Pertussis Vaccine; Placenta; Population; Pregnancy; Process; Property; Public Health; Recommendation; Respiratory Mucosa; Respiratory System; Respiratory Tract Infections; Respiratory tract structure; Role; Series; Testing; Tetanus Vaccine; Vaccinated; Vaccination; Vaccines; Whole Cell Vaccine; Work; antimicrobial; clinical efficacy; experimental study; high risk infant; improved; maternal vaccination; member; mortality; neonatal Fc receptor; novel; offspring; parenteral administration; pathogen; pertactin; pregnant; prevent; prophylactic; public health relevance; respiratory; response; trend

 DESCRIPTION (provided by applicant): B. pertussis causes a severe respiratory disease (whooping cough) in young infants associated with high mortality rates. The acellular pertussis vaccine has been part of the routine pediatric immunization schedule as a component of the Diphtheria-Tetanus vaccine (DTaP) for over two decades. Despite extensive vaccination, pertussis cases continue to emerge, the majority in infants <3 months of age who have not completed the primary vaccination series. One of the proposed reasons for this increased incidence has been the failure of the acellular pertussis vaccine to provide robust long-lasting protective immunity. On the basis of raising antibody levels in the population, immunization of mothers and other household members has been recommended to reduce exposure to young infants. The immune responses to the acellular pertussis vaccine elicited in infants and during pregnancy are not thoroughly known and firm correlates of protection remain to be established. A better understanding of protective immunity necessary to prevent B. pertussis infection is required to seek out more effective vaccines. IgA is commonly viewed as essential for protection against mucosal pathogens, but strong systemic IgG responses are generated following parenteral vaccination with DTaP in children and Tdap in adults; the same trend is seen in animal models. In this application we propose to study the role of vaccine-induced IgG in protection against B. pertussis in the context of both maternal and infant immunization and the mechanisms involved, specifically the antimicrobial capacity of anti-B. pertussis IgG and the processes involved in translocation through the mucosa and into the airways. We will test the hypothesis that maternal and infant vaccine-induced IgG actively transported through the respiratory mucosa via the neonatal Fc receptor (FcRn) deploys functional antimicrobial properties and mediates protection against B. pertussis infection. In Specific Aim 1, we will examine the contribution of pertussis-specific IgG induced through maternal vaccination and transferred to offspring via placenta and/or milk in protection against pertussis infection and examine the involvement of the FcRn in the transport of milk IgG from the intestinal lumen into circulation and of circulating IgG across epithelium in the respiratory tract and into the airways for protection against infection. In Specific Aim 2, we will examine the contribution of IgG produced in infants immunized with DTaP in protection against pertussis, their functional capacity and FcRn-mediated translocation to the respiratory airways. This work has the potential to identify a mechanism that can explain how IgG protects against B. pertussis infection.

 描述（由申请人提供）：百日咳博德特氏菌会导致幼儿出现严重的呼吸道疾病（百日咳），并导致高死亡率。无细胞百日咳疫苗已成为常规儿科免疫计划的一部分，作为白喉-破伤风疫苗的组成部分。 (DTaP) 尽管进行了广泛的疫苗接种，但百日咳病例仍在不断出现，其中大多数是未完成初级疫苗接种系列的婴儿。这种发病率的增加是由于无细胞百日咳疫苗未能提供强大的持久保护性免疫力，在提高人群抗体水平的基础上，建议母亲和其他家庭成员进行免疫接种，以减少幼儿的免疫暴露。婴儿和怀孕期间对无细胞百日咳疫苗的反应尚不完全清楚，需要更好地了解预防百日咳博德特氏菌感染所需的保护性免疫，以寻找更有效的疫苗。通常被认为对于预防粘膜病原体至关重要，但在儿童中接种 DTaP 并在成人中接种 Tdap 后，会产生强烈的全身 IgG 反应；在本应用中，我们建议研究疫苗诱导的作用。 IgG 在母体和婴儿免疫中预防百日咳博德特氏菌的作用及其相关机制，特别是抗百日咳博德特氏菌 IgG 的抗菌能力以及通过粘膜进入的过程。我们将测试以下假设：母婴疫苗诱导的 IgG 通过新生儿 Fc 受体 (FcRn) 主动转运通过呼吸道粘膜，发挥功能性抗菌特性并介导针对百日咳博德特氏菌感染的保护作用。检查通过母体疫苗接种诱导并通过胎盘和/或乳汁转移给后代的百日咳特异性 IgG 在预防百日咳感染方面的作用，并检查 FcRn 在乳汁运输中的参与IgG 从肠腔进入循环系统，以及循环 IgG 穿过呼吸道上皮进入气道以预防感染。在具体目标 2 中，我们将检查接受 DTaP 免疫的婴儿中产生的 IgG 在预防百日咳方面的贡献。这项工作有可能确定一种机制，可以解释 IgG 如何预防百日咳博德特氏菌感染。