A novel lipidic adjuvant carrier system for vaccination including vaccination via the oral route

我们开发了一种脂类-核心-多肽疫苗佐剂系统，该系统基于将脂氨基酸掺入到多功能部分中，为增强潜在的多肽疫苗的抗原性提供了一种很好的手段。由于该系统包含许多变量，可以进行实质性的修改，我们现在希望完全优化其结构配置。我们将在固相上合成一个间隔基-硫氨酸-多功能倍增体系的文库。将在这些不同的脂核系统上合成模型肽表位，并将抗体反应与耦合到传统疫苗载体上的模型肽表位的反应进行比较。包括微粒系统在内的脂核免疫原结构也将被口服，随后将测量血清免疫球蛋白反应和分泌型IgA。这种新的系统可以用于任何潜在的疫苗-多肽表位，并可以开辟一条现代疫苗接种的新途径。这些合成疫苗的具体优点包括疫苗的稳定性更好，重复性好，不使用有毒的常规佐剂。这个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。该系统提供免疫，反应风险较小，因为它只产生针对受感染微生物的抗体。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，以及在某些情况下刺激错误类型的免疫。口服疫苗的开发将使它们得到更广泛的获得，使患者能够自我管理，并显著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 Lipid-Core-Peptide vaccine adjuvant system, based on the incorporation of lipoamino acids into poly-functional moiety that provides an excellent means for enhancing the antigenicity of a potential peptide-vaccine. As the system contains many variables, which allow substantial modifications to be made, we now wish to fully optimise its structural configuration. A library of spacer-lipoamino acid-poly-functional multiplier systems will be synthesised on solid phase. Model peptide epitopes will be synthesised on these different lipid-core systems and the antibody response will be compared with the response of the model peptide epitopes coupled to conventional vaccine carriers. The Lipid-Core Immunogen constructs including particulate systems will be administered orally as well, followed by measurement of the serum IgG response and the secretory IgA. This novel system can be used for any potential vaccine-peptide epitope and can open a new route to modern vaccination. The specific advantages of these kind of synthetic vaccines include the greater stability of the vaccine, reproducibility, eliminate the use of toxic conventional adjuvants. The key to this system is a novel carrier construct, which is non-toxic and not immunogenic. The system confers immunity with smaller risk of reaction, since it generates antibody production only against the infective microorganism. 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 for skilled medical personnel, risk of HIV and other blood-borne diseases, restricted availability and, in cases, stimulation of the wrong type of immunity. Development of vaccines for oral administration will make them much more widely available, permitting self-administration by patients and markedly improving the operation of Public Health vaccination programs, particularly in developing countries.