Moyle Peter M, Olive Colleen, Ho Mei-Fong, Good Michael F, Toth Istvan
School of Pharmacy, The University of Queensland, St. Lucia 4072, Queensland, Australia.
J Med Chem. 2006 Oct 19;49(21):6364-70. doi: 10.1021/jm060475m.
We have developed a highly pure, self-adjuvanting, triepitopic Group A Streptococcal vaccine based on the lipid core peptide system, a vaccine delivery system incorporating lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity. Vaccine synthesis was performed using native chemical ligation. Due to the attachment of a highly lipophilic adjuvant, addition of 1% (w/v) sodium dodecyl sulfate was necessary to enhance peptide solubility in order to enable ligation. The vaccine was synthesized in three steps to yield a highly pure product (97.7% purity) with an excellent overall yield. Subcutaneous immunization of B10.BR (H-2(k)) mice with the synthesized vaccine, with or without the addition of complete Freund's adjuvant, elicited high serum IgG antibody titers against each of the incorporated peptide epitopes.
我们基于脂质核心肽系统开发了一种高纯度、自佐剂化的三表位A群链球菌疫苗，该脂质核心肽系统是一种将脂质佐剂、载体和肽表位整合到单个分子实体中的疫苗递送系统。疫苗合成采用天然化学连接法。由于连接了高度亲脂性佐剂，因此需要添加1%（w/v）的十二烷基硫酸钠来提高肽的溶解度，以便进行连接。疫苗分三步合成，得到了高纯度产品（纯度97.7%），总产率优异。用合成疫苗对B10.BR（H-2(k)）小鼠进行皮下免疫，无论是否添加完全弗氏佐剂，均可诱导出针对每个掺入肽表位的高血清IgG抗体滴度。
