A Bioengineerable Self-adjuvating Nanoparticle for Antigen Delivery

用于抗原递送的生物工程自辅助纳米颗粒

基本信息

批准号：
8570051
负责人：
SHILADITYA DASSARMA
金额：
$ 7.68万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-25 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8570051
关键词：
Acute Address Adjuvant Animals Antigens Archaea Area Attenuated Bacterial Antigens Baltimore Bioinformatics Biological Biomedical Engineering Biotechnology Bone Marrow Caliber Cells Cessation of life Child Code Collaborations Communicable Diseases Country Cytolysis Data Developing Countries Development Disease Disease Outbreaks Drug Formulations Effectiveness Evaluation Fever Food Foundations Gallbladder Gases Gene Cluster Genetic Engineering Goals Gut associated lymphoid tissue Human Immune response Immunization Immunology Inbred BALB C Mice Individual Infant Infection Institutes International Lead Length Letters Licensing Life Liver Local Anti-Infective Agents Love Maryland Membrane Methods Microbiology Morbidity - disease rate Mus Oral Oral Administration Organism Paratyphoid Fever Plasmids Prevention Property Proteins Recombinants Refrigeration Route Safety Salmonella Salmonella Vaccines Salmonella enterica Salmonella typhi Sampling Sanitation Science Scientist Shapes Sodium Chloride Spleen Surface System Temperature Testing Typhoid Fever Universities Vaccine Antigen Vaccines Vesicle Viral Virulent Water Work base comparative efficacy testing gas vesicle protein immunogenic improved intraperitoneal mortality mouse model nanoparticle novel novel strategies oral vaccine particle pathogen polypeptide protective efficacy public health relevance response vaccine candidate vaccine delivery vaccinology wasting

项目摘要

DESCRIPTION (provided by applicant): A unique vaccine platform employs novel bioengineerable nanoparticles, Haloarchaeal gas vesicles (HGVs), as an adjuvant and antigen delivery system that is inexpensive, effective, and shelf-stable (requiring no refrigeration). When administered to animals, HGV nanoparticles with surface-displayed antigens produce strong long-lived immune responses. In previous work, antigens from bacterial and viral pathogens were expressed as a fusion to one of the HGV protein components and in all cases the recombinant HGVs were highly immunogenic in mice. We plan to test the effectiveness of HGVs as a vaccine vehicle against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. These human pathogens remain important causes of morbidity and mortality in many countries as a result of poor sanitation, and water and food contaminated by human fecal waste. Our goal is to progress toward the development of a safe and inexpensive oral vaccine against invasive Salmonella disease that can be used in both the developing and developed world. We propose to: (a) produce multiple Salmonella protective antigens displayed on HGV nanoparticles; and (b) deliver the bioengineered HGV-vaccine antigen nanoparticles and determine their protective efficacy in a mouse model. We will also perform more in-depth immunological analyses and test protection using combinations of HGV formulations. These studies will lay the foundation for subsequent evaluation of this approach in humans as well as customize the system for prevention of other diseases. The development of a safe, oral adjuvant and vaccine delivery vehicle which is inexpensive, effective, and shelf-stable should lead to a global revolution in the prevention of infectious diseases.

描述（由申请人提供）：独特的疫苗平台采用新型生物工程纳米颗粒、盐古菌气体囊泡（HGV）作为佐剂和抗原递送系统，该系统廉价、有效且货架稳定（无需冷藏）。什么时候将带有表面展示抗原的 HGV 纳米颗粒给予动物后，会产生强烈的、持久的免疫反应。在之前的工作中，来自细菌和病毒病原体的抗原被表达为与一种 HGV 蛋白成分的融合体，并且在所有情况下，重组 HGV 在小鼠中都具有高度免疫原性。我们计划测试 HGV 作为疫苗载体对抗伤寒沙门氏菌血清型伤寒的有效性。由于卫生条件差以及水和食物被人类粪便污染，这些人类病原体仍然是许多国家发病和死亡的重要原因。我们的目标是开发一种安全且廉价的口服疫苗，以预防侵袭性沙门氏菌疾病，该疫苗可用于发展中国家和发达国家。我们建议：（a）生产多种沙门氏菌保护性抗原，展示在 HGV 纳米颗粒上； (b) 递送生物工程 HGV 疫苗抗原纳米颗粒并确定其在小鼠模型中的保护功效。我们还将使用 HGV 制剂组合进行更深入的免疫学分析和测试保护。这些研究将为后续在人类中评估这种方法以及定制预防其他疾病的系统奠定基础。开发一种安全、廉价、有效且储存稳定的口服佐剂和疫苗输送载体应该会引发一场预防传染病的全球革命。