Centre for International Child Health, University of Melbourne, Melbourne, Victoria, Australia.
Curr Opin Infect Dis. 2009 Dec;22(6):544-52. doi: 10.1097/QCO.0b013e328332bbfe.
This review provides an overview of progress of the development of group A streptococcal (GAS) vaccines with a focus on recent advances.
Historically, GAS vaccine development has focused on the N-terminus of the M protein, which ultimately led to successful phase I/II clinical trials of a 26-valent recombinant M protein vaccine in 2004-2005. More recently, interest in antigens conserved among most, if not all, group A streptococci has increased. However, no vaccines containing these antigens have reached clinical trials. Three strategies have been used to develop conserved antigen vaccine candidates: use of the conserved region of the M protein; use of well described virulence factors as antigens, including streptococcal C5a peptidase, streptococcal carbohydrate, fibronectin-binding proteins, cysteine protease and streptococcal pili; and use of reverse vaccinology to identify novel antigens.
Several vaccine candidates against GAS infection are in varying stages of preclinical and clinical development. Although there is great hope that one of these vaccine candidates will reach licensure in the next decade, only one, the multivalent N-terminal vaccine, has entered clinical trials in the last 30 years. Although strong advocacy for GAS vaccine development is important, there remains an urgent need to institute available public health control measures against GAS diseases globally, particularly in developing countries.
本综述概述了 A 组链球菌(GAS)疫苗的发展进展,重点介绍了最近的进展。
从历史上看,GAS 疫苗的开发一直集中在 M 蛋白的 N 端,这最终导致了 2004-2005 年 26 价重组 M 蛋白疫苗的 I/II 期临床试验的成功。最近,人们对大多数(如果不是全部)A 组链球菌之间具有保守性的抗原越来越感兴趣。然而,没有含有这些抗原的疫苗进入临床试验。已经使用了三种策略来开发保守抗原疫苗候选物:使用 M 蛋白的保守区域;使用描述良好的毒力因子作为抗原,包括链球菌 C5a 肽酶、链球菌碳水化合物、纤维蛋白结合蛋白、半胱氨酸蛋白酶和链球菌菌毛;以及使用反向疫苗学来鉴定新抗原。
有几种针对 GAS 感染的疫苗候选物处于不同的临床前和临床开发阶段。尽管人们非常希望这些疫苗候选物中的一种在未来十年内获得许可,但在过去 30 年中,只有一种多价 N 端疫苗进入了临床试验。尽管大力倡导开发 GAS 疫苗很重要,但仍迫切需要在全球范围内实施针对 GAS 疾病的现有公共卫生控制措施,特别是在发展中国家。