Immuno-Proteomic Approach to Anti-Tick Vaccine Development

抗蜱疫苗开发的免疫蛋白质组学方法

• 批准号: 8378742
• 负责人: Thomas N Mather
• 金额: $ 29.53万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8378742
• 关键词: Adjuvant; Affect; Affinity; Antibodies; Antigens; Arthropod Vectors; Back; Basophils; Binding; Bioinformatics; Bioterrorism; Bite; Black-legged Tick; Blood; Cavia; Cellular Immunity; Complementary DNA; Computer software; DNA; Databases; Dermal; Development; Disease; Domestic Animals; Emerging Communicable Diseases; Epitope Mapping; Epitopes; Erythema; Excision; Felis catus; Fingerprint; Gene Expression Profile; Genes; Genetic; HLA Antigens; Human; IgE; Immune; Immune Sera; Immune response; Immunity; Immunization; Immunology; Immunotherapeutic agent; Impairment; In Situ; Individual; Infection; Informatics; Intervention; Investigation; Liquid Chromatography; Maps; Mass Spectrum Analysis; Measures; Methods; Mining; Modeling; Patients; Peptides; Proteins; Proteomics; Public Health; Reaction; Recombinant Proteins; Research; Resistance; Role; Route; Saliva; Salivary; Salivary Glands; Salivary Proteins; Sampling; Site; Solutions; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spottings; Symptoms; T-Lymphocyte; Tick-Borne Diseases; Ticks; Translations; Trypsin; Two-Dimensional Gel Electrophoresis; Vaccination; Vaccine Antigen; Vaccine Design; Vaccines; Vector-transmitted infectious disease; base; biodefense; cytokine; design; disease transmission; feeding; fighting; human subject; immunogenic; immunogenicity; improved; in vitro testing; innovation; novel; pathogen; potency testing; prevent; response; sound; tool; transmission process; two-dimensional; vaccination strategy; vaccine candidate; vaccine development

Various species of ticks carry more than 20 pathogens, including Cat A-C and emerging/re-emerging agents, all capable of causing significant disease in humans, making targeting the tick instead of each individual pathogen a sound intervention strategy. Tick salivary molecules modulate host innate and adaptive immune defenses, naturally facilitating both tick feeding and pathogen transmission. In particular, blood feeding by the tick Ixodes scapularis polarizes responses in host T lymphocytes resulting in a strongly Th2 cytokine profile, while acquired tick resistance (ATR), a phenomenon associated with tick rejection and pathogen transmission impairment, is associated with Th1 cytokines. This proposal is based on the hypothesis that a vaccination strategy evoking a robust ATR response in hosts also will provide protection against tick-borne pathogen transmission. Using state-of-the-art informatics and proteomics methods, our primary objective is to identify vaccine candidates from tick transcriptomes predicted to stimulate robust antibody- and cellmediated immunity in humans. New information will be gathered regarding correlates of immunity to tick salivary molecules in humans, and potential correlates of protection against tick-borne pathogen transmission in a Guinea pig (GP) model. In aim 1, bioinformatics, epitope mapping tools, and microarrays, are used to identify, isolate and characterize critical antigens from the I. scapularis salivome and design epitope-based vaccines that stimulate: 1) Th1 polarization in PBMCs derived from tick-sensitized patients, and 2) ATR in a GP model of pathogen transmission. In aim 2, we use high throughput proteomic tools to similarly identify and isolate tick molecules reactive with IgE antibodies that elicit basophil degranulation resulting in an immediate-type dermal erythema/itch reaction at the tick bite site. The third aim includes measuring symptoms and immune correlates of ATR in sensitized humans challenged with pathogen-free ticks. Additionally, it combines findings from the first two aims and evaluates a bi-valent tick-borne disease transmission vaccine strategy in GPs. This project's innovation is in its application of a novel broad spectrum platform for vaccine design expected to significantly enhance translation of a "gene to vaccine" strategy to humans.

不同种类的蜱虫携带20多种病原体，包括A-C类和新出现/再出现的病原体，