Glycoconjugate Nanoparticle Vaccines Against Burkholderia Infections

针对伯克霍尔德氏菌感染的糖复合物纳米颗粒疫苗

基本信息

批准号：
9186787
负责人：
Alfredo G Torres
金额：
$ 38.75万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9186787
关键词：
Adjuvant Aerosols Animals Antibiotics Antigens Area Attention Bacteria Biological Biological Markers Biological Warfare Bioterrorism Burkholderia Burkholderia Infections Burkholderia mallei Burkholderia pseudomallei CD4 Positive T Lymphocytes Characteristics Coupled Cutaneous DNA DNA Vaccines Data Development Disease Disease Progression Dose Endemic Diseases Formulation Foundations Generations Glanders Glycoconjugates Goals Gold Human Immune Immune response Immunity Immunization Immunocompromised Host Immunoglobulin G Immunologics Infection Inflammatory Ingestion Licensing Melioidosis Memory B-Lymphocyte Modeling Mus Nature Opportunistic Infections Organism Outcome Pathology Polysaccharides Population Populations at Risk Prevention Procedures Process Property Proteins Public Health Research Serological Serum System T-Lymphocyte Subsets Testing Toxic effect Vaccination Vaccines Whole Cell Vaccine Work base biothreat capsule clinically relevant combat cost cost effective cytokine diabetic efficacy testing flexibility human disease immunogenic in vivo innovation insight mouse model nanoparticle nanovaccine novel pathogen prevent prophylactic research study therapeutic vaccine vaccination strategy vaccine development weapons

项目摘要

Burkholderia mallei and B. pseudomallei are bacterial pathogens and causative agents of glanders and melioidosis, respectively. At present, effective vaccines for prevention of glanders or meliodosis have not been developed. However, renewed attention has been directed toward development of Burkholderia vaccines because of the pathogens' seemingly ideal characteristics for malicious use as a biowarfare weapon. Additionally, a vaccine will also have significant value for the immunization of at-risk populations in melioidosis/glanders endemic areas of the world. Therefore, our long-term goal is to develop a platform that allows for the efficient generation of a multicomponent vaccine which is able to protect against both glanders and melioidosis. Our approach will use glycoconjugates coupled to gold nanoparticles (NP) and test their protective properties in clinically relevant models of infection. The central hypothesis tested indicates that protein antigens of B. mallei or B. pseudomallei coupled to NP polysaccharides will elicit protection in relevant mammalian species, and that these antigens will correlate with clinically important serologic/immunologic readouts. The hypothesis will be evaluated by developing different protein-polysaccharide NPs and comparing their efficacy in vivo. The flexible NP platform will allow us to additionally incorporate novel antigens identified by other groups as further enhancing protective immunity. We will establish an optimal immunization procedure and test the efficacies of protein-polysaccharide NPs in a clinically relevant and highly controlled aerosol murine model of infection. Finally, we aim to identify the correlates/biomarkers of protection induced by protein- polysaccharide NP vaccination. This proposal is innovative because it capitalizes on the use of a subunit-NP vaccine, which could be easily licensable because of its lower cost and more widely disseminated vaccinations for at-risk populations. Together, these outcomes will help us to identify correlates of protection from protein- polysaccharide nanoparticles and provide optimized vaccination strategies.

鼻疽伯克霍尔德氏菌和类鼻疽伯克霍尔德氏菌是细菌病原体，也是鼻疽和鼻疽的病原体。分别是类鼻疽。目前，尚未研制出有效的疫苗来预防鼻疽或类鼻疽。发达。然而，人们重新关注伯克霍尔德杆菌疫苗的开发因为病原体似乎具有恶意用作生物战武器的理想特征。此外，疫苗对于高危人群的免疫也具有重要价值。世界类鼻疽/鼻疽流行区。因此，我们的长期目标是开发一个平台允许有效生成能够预防两种鼻疽的多组分疫苗和类鼻疽。我们的方法将使用与金纳米粒子 (NP) 偶联的糖复合物并测试其临床相关感染模型中的保护特性。检验的中心假设表明鼻疽或拟鼻疽的蛋白质抗原与 NP 多糖偶联将在相关方面引起保护哺乳动物物种，并且这些抗原将与临床上重要的血清学/免疫学相关读数。该假设将通过开发不同的蛋白质-多糖纳米颗粒并进行比较来评估它们在体内的功效。灵活的 NP 平台将使我们能够额外整合已识别的新抗原被其他群体视为进一步增强保护性免疫力。我们将建立最佳的免疫程序并测试蛋白质-多糖纳米粒子在临床相关且高度受控的气溶胶中的功效小鼠感染模型。最后，我们的目标是确定蛋白质诱导的保护的相关性/生物标志物多糖NP疫苗接种。该提案具有创新性，因为它利用了亚基-NP 疫苗，由于成本较低且疫苗接种范围更广，因此很容易获得许可对于高危人群。总之，这些结果将帮助我们确定蛋白质保护的相关性多糖纳米颗粒并提供优化的疫苗接种策略。