Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Nat Commun. 2016 Nov 22;7:13473. doi: 10.1038/ncomms13473.
Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept 'neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.
病毒亚单位疫苗通常包含免疫优势的非中和表位，这些表位会改变宿主的免疫反应。在疫苗设计中应消除这些表位，但目前还没有可靠的方法来评估表位诱导中和免疫反应的能力。在这里，我们引入了一个新的概念“中和免疫原性指数”（NII）来评估表位的中和免疫原性。为了确定 NII，我们用聚糖探针掩盖表位，然后评估该表位对疫苗整体中和免疫原性的贡献。作为概念验证，我们测量了由中东呼吸综合征冠状病毒（MERS-CoV）受体结合域组成的免疫原上不同表位的 NII。此外，我们通过掩盖具有负 NII 评分的表位来设计这种疫苗的变体形式。这种工程疫苗在保护转基因小鼠免受致命性 MERS-CoV 攻击方面表现出显著的功效增强。我们的研究可能为设计针对 MERS-CoV 和其他危及生命的病毒的高效亚单位疫苗提供指导。
