Department of Chemistry, Division of Applied Microbiology, Lund University, Lund, Sweden
Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Lund, Sweden.
Microbiol Mol Biol Rev. 2020 Nov 25;85(1). doi: 10.1128/MMBR.00078-20.
Vaccines work primarily by eliciting antibodies, even when recovery from natural infection depends on cellular immunity. Large efforts have therefore been made to identify microbial antigens that elicit protective antibodies, but these endeavors have encountered major difficulties, as witnessed by the lack of vaccines against many pathogens. This review summarizes accumulating evidence that subdominant protein regions, i.e., surface-exposed regions that elicit relatively weak antibody responses, are of particular interest for vaccine development. This concept may seem counterintuitive, but subdominance may represent an immune evasion mechanism, implying that the corresponding region potentially is a key target for protective immunity. Following a presentation of the concepts of immunodominance and subdominance, the review will present work on subdominant regions in several major human pathogens: the protozoan , two species of pathogenic streptococci, and the dengue and influenza viruses. Later sections are devoted to the molecular basis of subdominance, its potential role in immune evasion, and general implications for vaccine development. Special emphasis will be placed on the fact that a whole surface-exposed protein domain can be subdominant, as demonstrated for all of the pathogens described here. Overall, the available data indicate that subdominant protein regions are of much interest for vaccine development, not least in bacterial and protozoal systems, for which antibody subdominance remains largely unexplored.
疫苗主要通过激发抗体起作用，即使从自然感染中恢复依赖于细胞免疫也是如此。因此，人们已经做出了巨大的努力来识别能够激发保护性抗体的微生物抗原，但这些努力遇到了重大困难，许多病原体都缺乏疫苗就是明证。这篇综述总结了越来越多的证据表明，亚显性蛋白区域（即暴露于表面、引发相对较弱抗体反应的区域）对于疫苗开发特别有意义。这个概念似乎有违直觉，但亚显性可能代表一种免疫逃避机制，这意味着相应的区域可能是保护性免疫的关键靶标。在介绍免疫显性和亚显性的概念之后，本综述将介绍几种主要人类病原体中亚显性区域的工作：原生动物、两种致病性链球菌以及登革热病毒和流感病毒。后面的部分专门讨论亚显性的分子基础、其在免疫逃避中的潜在作用以及对疫苗开发的一般意义。特别强调的是，整个暴露于表面的蛋白域都可以是亚显性的，正如这里描述的所有病原体所证明的那样。总的来说，现有数据表明，亚显性蛋白区域对于疫苗开发非常有意义，尤其是在细菌和原生动物系统中，抗体的亚显性在很大程度上仍未得到探索。
