A multiple antigen lipophilic adjuvant carrier (MALAC) system

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多功能核心，为增强潜在肽疫苗的抗原性提供了一种极好的手段。一种用于产生抗体而不使用任何常规佐剂的系统。该系统包括两种或更多种不同的抗原和一种或多种脂质锚。该系统的关键是一种新型的载体结构，它是无毒和无免疫原性的。该系统包含变量，允许优化其结构配置。多功能MALAC系统的小文库将以结合溶液或固相技术的受控逐步方式合成，其中构建体的确切化学结构（和不同免疫肽序列的顺序）是预先确定的。将抗原性和对疾病的保护与使用常规疫苗载体产生的抗原性和保护进行比较。我们还旨在利用脂肽两亲物的颗粒形成特性，以形成微粒口服抗原，利用GALT或其他肠道部位从胃肠道摄取颗粒的现象。将口服给予MALAC构建体，然后测量血清IgG。通过口服途径的疫苗接种是非常理想的，因为它可以克服注射给药固有的许多缺点，例如患者接受性差、需要熟练的医务人员、HIV和其他血液传播疾病的风险、有限的可用性以及有时刺激错误类型的免疫。口服疫苗的开发使其更广泛地获得，允许自我管理并改善公共卫生疫苗接种计划的运作，特别是在发展中国家。

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.