Olive Colleen, Ho Mei-Fong, Dyer Joanne, Lincoln Douglas, Barozzi Nadia, Toth Istvan, Good Michael F
Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Australia.
J Infect Dis. 2006 Jun 15;193(12):1666-76. doi: 10.1086/504266. Epub 2006 May 10.
The development of a vaccine to prevent infection with group A streptococcus (GAS) is hampered by the widespread diversity of circulating GAS strains and M protein types, and it is widely believed that a multivalent vaccine would provide better protective immunity.
We investigated the efficacy of incorporating 3 M protein serotypic amino-terminal epitopes from GAS isolates that are common in Australian Aboriginal communities and a conformational epitope from the conserved carboxy-terminal C-repeat region into a single synthetic lipid core peptide (LCP) vaccine construct in inducing broadly protective immune responses against GAS after parenteral delivery to mice.
Immunization with the tetraepitopic LCP vaccine construct led to high titers of systemic, antigen-specific IgG responses and the induction of broadly protective immune responses, as was demonstrated by the ability of immune serum to opsonize multiple GAS strains. Systemic challenge of mice with a lethal dose of GAS given 60 or 300 days after primary immunization showed that, compared with the control mice, the vaccinated mice were significantly protected against GAS infection, demonstrating that the vaccination stimulated long-lasting protective immunity.
These data support the efficacy of the LCP vaccine delivery system in the development of a synthetic, multiepitopic vaccine for the prevention of GAS infection.
A群链球菌（GAS）循环菌株和M蛋白类型的广泛多样性阻碍了预防GAS感染疫苗的研发，人们普遍认为多价疫苗能提供更好的保护性免疫。
我们研究了将来自澳大利亚原住民社区常见的GAS分离株的3种M蛋白血清型氨基末端表位以及保守的羧基末端C重复区域的一个构象表位整合到单个合成脂质核心肽（LCP）疫苗构建体中，经肠胃外途径给小鼠接种后诱导针对GAS产生广泛保护性免疫反应的效果。
用四表位LCP疫苗构建体免疫导致产生高滴度的全身性、抗原特异性IgG反应，并诱导产生广泛的保护性免疫反应，免疫血清对多种GAS菌株进行调理的能力证明了这一点。在初次免疫后60天或300天用致死剂量的GAS对小鼠进行全身性攻击，结果显示，与对照小鼠相比，接种疫苗的小鼠受到显著保护，免受GAS感染，这表明接种疫苗激发了持久的保护性免疫。
这些数据支持LCP疫苗递送系统在研发用于预防GAS感染的合成多表位疫苗方面的有效性。
