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（由应用提供）：B。百日咳导致与高死亡率相关的年轻婴儿的严重呼吸道疾病（百日咳）。二十多年来，细胞细胞百日咳疫苗已成为常规小儿免疫计划的一部分。尽管疫苗广泛，但百日咳病例仍在出现，婴儿少于3个月大的婴儿尚未完成初级疫苗接种系列。提出这种发病率的提议原因之一是细胞百日咳疫苗无法提供强大的长期保护性免疫。在提高人群中的抗体水平的基础上，建议母亲和其他家庭成员免疫以减少对年轻婴儿的接触。对婴儿和怀孕期间引起的细胞百日咳疫苗的免疫反应尚不清楚，并且固件相关的保护尚待确定。需要更好地了解防止百日咳感染所需的保护性免疫，以寻找更有效的疫苗。通常认为IgA对于防止粘膜病原体的保护至关重要，但是在儿童DTAP和成人TDAP的父母疫苗后，产生了强大的全身IgG反应。在动物模型中也看到了同样的趋势。在此应用中，我们建议研究在母子和婴儿免疫和所涉及的机制的背景下，疫苗诱导的IgG在防御百日咳中的作用，特别是抗B的抗微生物能力。百日咳IgG和通过粘膜转运并进入气道所涉及的过程。我们将检验以下假设：母子和婴儿疫苗诱导的IgG通过新生儿FC受体（FCRN）部署功能性抗菌特性并介导保护B. tittussis感染。在特定目标1中，我们将研究通过材料疫苗接种诱导的百日咳特异性IgG的贡献，并通过安置和/或牛奶转移到后代和/或牛奶中，以防止震颤感染和检查FCRN参与牛奶IgG从肠道中的运输中，从肠道中循环和循环IgG跨循环互动，并在跨性别范围内进行了互动。在特定的目标2中，我们将研究用DTAP免疫的婴儿中产生的IgG的贡献，其功能能力以及FCRN介导的易位对呼吸道气道。这项工作有可能确定可以解释IgG如何预防百日咳感染的机制。