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

• 批准号: 9282736
• 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
• 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/9282736
• 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; Clinical; 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; Pathogenicity; Pathology; Polysaccharides; Population; Populations at Risk; Prevention; Preventive vaccine; Procedures; Process; Property; Proteins; Public Health; Research; Serological; Serum; System; Testing; Toxic effect; Vaccination; Vaccines; Whole Cell Vaccine; Work; biothreat; capsule; clinically relevant; combat; cost; cost effective; cytokine; diabetic; efficacy testing; experimental study; flexibility; human disease; immunogenic; in vivo; innovation; insight; mouse model; nanoparticle; nanovaccine; novel; pathogen; prevent; therapeutic vaccine; vaccination strategy; vaccine development; weapons

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.

Burkholderia Mallei和B. pseudomallei是细菌病原体和腺体的致病性。 分别是Melioidosis。目前，预防腺体或混血病的有效疫苗尚未 发达。但是，重新关注的关注是针对Burkholderia疫苗开发的 由于病原体看似理想的特征，可将恶意用作生物处理武器。 此外，疫苗还将具有重要的价值 Melioidosis/腺体流行地区。因此，我们的长期目标是开发一个平台 允许有效地生成能够防止两个腺体的多组分疫苗 和黑梅利病。我们的方法将使用与金纳米颗粒（NP）耦合的糖缀合物并测试其 临床相关模型感染模型中的保护特性。测试的中央假设表明 与NP多糖耦合的麦芽芽孢杆菌或假叶芽孢杆菌的蛋白质抗原将在相关方面提供保护 哺乳动物物种，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 - 糖糖NP并进行比较来评估该假设 他们在体内的功效。灵活的NP平台将允许我们另外掺入已识别的新型抗原 其他群体作为进一步增强的保护性免疫力。我们将建立最佳的免疫程序 并测试蛋白质 - 糖糖NP在临床相关且高度控制的气溶胶中的效率 鼠类感染模型。最后，我们旨在确定蛋白质引起的保护的相关/生物标志物 多糖NP疫苗接种。该提议具有创新性，因为它利用了使用亚基-NP 疫苗，由于其成本较低和更广泛的疫苗接种，因此很容易获得许可 对于高危人群。这些结果在一起将有助于我们确定保护免受蛋白质的相关性 - 多糖纳米颗粒并提供优化的疫苗接种策略。