A multiple antigen lipophilic adjuvant carrier (MALAC) system

多抗原亲脂性佐剂载体（MALAC）系统

• 批准号: nhmrc : 252733
• 负责人: Prof Istvan Toth
• 金额: $ 9.44万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/multiple-antigen-lipophilic-carrier-malac/81745
• 关键词: multiple; antigen; lipophilic; adjuvant; carrier

We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and non-immunogenic. The system contains variables, which allow optimising its structural configuration. A small library of poly-functional MALAC system will be synthesised in a controlled step-by-step way combining solution or solid phase techniques, where the exact chemical structure (and the order of the different immunological peptide sequences) of the construct is pre-determined. The antigenicity and the protection against disease will be compared with antigenicity and protection generated using conventional vaccine carriers. We also aim to exploit the particulate-forming properties of the lipo-peptide amphiphiles, to form micro-particulate oral antigens, exploiting the phenomenon of particulate uptake from the GI tract by the GALT or other intestinal sites. The MALAC constructs will be administered orally followed by the measurement of the serum IgG. Vaccination via the oral route is highly desirable, since it can overcome many of the disadvantages inherent in administration by injection - e.g. poor patient acceptability, requirement of skilled medical personnel, risk of HIV and other blood-born diseases, restricted availability and sometimes, stimulation of the wrong type of immunity. Development of vaccines for oral administration make them much more widely available, permitting self-administration and improving the operation of Public-Health vaccination programs, particularly in developing countries.

我们开发了一种多抗原-亲脂-佐剂-载体(Malac)系统，该系统基于将脂氨基酸掺入到一个多功能核心中，为增强潜在的多肽疫苗的抗原性提供了一个很好的手段。一种系统用于产生抗体，而不使用任何常规佐剂。该系统包括两个或多个不同的抗原和一个或多个脂锚。该系统的关键是一种新型的、无毒、无免疫原性的载体结构。该系统包含各种变量，可以优化其结构配置。一个多功能马来酸系统的小型文库将以受控的方式逐步结合溶液或固相技术合成，其中构建的确切化学结构(以及不同免疫学肽序列的顺序)是预先确定的。抗原性和对疾病的保护将与使用传统疫苗载体产生的抗原性和保护进行比较。我们还打算利用脂肽两亲分子的颗粒形成特性，利用GALT或其他肠道部位从胃肠道摄取颗粒的现象，形成微小颗粒口服抗原。将口服马来酸树脂构建物，然后测量血清免疫球蛋白。通过口服途径接种疫苗是非常可取的，因为它可以克服注射接种固有的许多缺点--例如，患者接受性差、对熟练医务人员的要求、艾滋病毒和其他血液传播疾病的风险、可获得性有限，有时还会刺激错误类型的免疫。口服疫苗的发展使其更广泛地可用，允许自我管理并改善公共卫生疫苗接种方案的运作，特别是在发展中国家。