Immune Responses to Biodefense Vaccines Early in Life

生命早期对生物防御疫苗的免疫反应

基本信息

批准号：
8127368
负责人：
Marcela F Pasetti
金额：
$ 4.78万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-23 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8127368
关键词：
Achyrocline Adjuvant Adult Aerosols Age Anthrax Attack Anthrax Vaccines Antibodies Antigens Area Attenuated Bacillus anthracis Bacillus anthracis spore Bacteria Bioterrorism Biothrax Cell Maturation Cell Separation Cell physiology Cellular Immunity Child Childhood Color Data Dendritic Cells Development Diphtheria Disease Distress Dose Elderly Emergency Situation Equilibrium Event Flagella Flow Cytometry Generations Goals Hepatitis B Human Immune Immune response Immune system Immunity Immunization Immunocompromised Host In Vitro Individual Infant Infection Knowledge Life Link Lipopolysaccharides Mails Maternal antibody Mediating Military Personnel Modeling Mothers Mus Natural Immunity Neonatal Newborn Infant Organism Pertussis Plague Plasmids Population Production Property Public Health Readiness Regimen Relative (related person)Research Research Personnel Risk Safety Salmonella Salmonella Vaccines Salmonella typhi Subunit Vaccines System T memory cell T-Cell Activation Tern Testing Tetanus Time Tissues United States Vaccinated Vaccination Vaccine Antigen Vaccines Virulent Vulnerable Populations Yersinia pestis abstracting adaptive immunity age group base biodefense capsule cell mediated immune response cytokine high risk immune function immunogenic immunogenicity improved in vivo mouse model neonate oral vaccine pathogen physical conditioning preclinical study prevent programs protective efficacy pup response tool vaccine candidate vaccine delivery vaccine development vector vector vaccine weapons

Achyrocline Adjuvant Adult Aerosols Age Anthrax Attack Anthrax Vaccines Antibodies Antigens Area Attenuated Bacillus anthracis Bacillus anthracis spore Bacteria Bioterrorism Biothrax Cell Maturation Cell Separation Cell physiology Cellular Immunity Child Childhood Color Data Dendritic Cells Development Diphtheria Disease Distress Dose Elderly Emergency Situation Equilibrium Event Flagella Flow Cytometry Generations Goals Hepatitis B Human Immune Immune response Immune system Immunity Immunization Immunocompromised Host In Vitro Individual Infant Infection Knowledge Life Link Lipopolysaccharides Mails Maternal antibody Mediating Military Personnel Modeling Mothers Mus Natural Immunity Neonatal Newborn Infant Organism Pertussis Plague Plasmids Population Production Property Public Health Readiness Regimen Relative (related person)Research Research Personnel Risk Safety Salmonella Salmonella Vaccines Salmonella typhi Subunit Vaccines System T memory cell T-Cell Activation Tern Testing Tetanus Time Tissues United States Vaccinated Vaccination Vaccine Antigen Vaccines Virulent Vulnerable Populations Yersinia pestis abstracting adaptive immunity age group base biodefense capsule cell mediated immune response cytokine high risk immune function immunogenic immunogenicity improved in vivo mouse model neonate oral vaccine pathogen physical conditioning preclinical study prevent programs protective efficacy pup response tool vaccine candidate vaccine delivery vaccine development vector vector vaccine weapons

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项目摘要

Bioterrorism is no longer a threat in the United States, but a reality. In 2001, the spread of anthrax spores through the U.S. mail illustrated that deadly agents can be acquired and spread using relatively unsophisticated means. It also highlighted our vulnerability to such attacks and the urgency for preparedness. Vaccine-induced protective immunity to potential bioterror weapons could be one of the most effective biodefense strategies. Most of the biodefense vaccines available have been tailored for military personnel (healthy adults). The civilian population in need of protection, however, includes people of all ages and physical conditions (newborns, infants, immunocompromised and the elderly), who are at greater risk and could become the enemy's sinister targets to inflict more casualties. Clearly, there is an urgent need for safe and effective vaccines for these highly vulnerable groups. We propose to evaluate protective efficacy of a new generation of biodefense vaccines based on attenuated Salmonella as a live vector to mucosally deliver protective antigens from Yersinia pestis and Bacillus anthracis. Our first goal is to determine whether these Salmonella biodefense vaccines are well tolerated and induce long-lasting protective immunity using a neonatal mouse model of immunogenicity that closely resembles the responses in humans. Based on preliminary data, we hypothesize that 1) Salmonella live vectors will be highly immunogenic in newborn mice; and 2) antibody and cell-mediated immunity will be induced despite the presence of maternal antibodies. We also aim to explore the mechanisms involved in the induction of neonatal adaptive immunity to Salmonella and encoded foreign antigens. Although neonatal responses to vaccines are usually feeble and Th2 biased, our preliminary data suggest that Salmonella-based biodefense vaccines can induce potent (adult-like) and balanced Th1/Th2- type responses in newborns despite the presence of maternal antibodies. We hypothesize that this is linked to the the capacity of the bacteria to induce neonatal dendritic cell maturation and T cell activation. This research will be highly relevent to public health as it will enable us to identify biodefense vaccines that can be safe and protect children and infants against bioterror weapons. It will also provide knowledge to better understand the mechanisms mediating neonatal-infant immunity to develop more effectivevaccines to prevent diseases early in life.

生物恐怖主义不再是美国的威胁，而是现实。 2001年，炭疽孢子的传播通过美国邮件说明，可以使用相对的致命代理人获取和传播不老练的手段。它还强调了我们对此类攻击的脆弱性和准备。疫苗引起的对潜在生物侵害武器的保护性免疫可能是最多的武器之一有效的生物形式策略。大多数可用的生物污染疫苗都是为军事量身定制的人员（健康成年人）。但是，需要保护的平民包括所有人年龄和身体状况（新生儿，婴儿，免疫功能低下和老年人）风险，可能成为敌人的险恶目标，以造成更多的伤亡。显然，迫切需要对于这些高度脆弱的群体来说，安全有效的疫苗。我们建议评估保护性新一代的生物化疫苗基于衰减沙门氏菌作为活载体的功效粘膜从鼠疫耶尔森氏菌和炭疽芽孢杆菌提供保护性抗原。我们的第一个目标是确定这些沙门氏菌生物化疫苗是否耐受性良好并诱导持久使用与反应相似的免疫原性模型的新生小鼠模型的保护性免疫力在人类中。根据初步数据，我们假设1）沙门氏菌活载体将很高新生小鼠的免疫原性； 2）尽管有抗体和细胞介导的免疫力孕产妇抗体的存在。我们还旨在探索诱导的机制对沙门氏菌和编码外抗原的新生儿适应性免疫。尽管新生儿对疫苗通常微弱，Th2有偏见，我们的初步数据表明基于沙门氏菌的生物粉丝疫苗可以诱导新生儿的有效（成人）和平衡的Th1/Th2型反应孕产妇抗体的存在。我们假设这与细菌的能力有关诱导新生儿树突状细胞成熟和T细胞活化。这项研究将与公众高度相关健康将使我们能够识别可以安全并保护儿童和婴儿的生物性疫苗反对生物武器。它还将提供知识以更好地了解介导的机制新生儿侵袭性的免疫力发展更有效的vaccines，以预防生命早期疾病。