Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines

Lanying Du, Wanbo Tai, Yang Yang, Guangyu Zhao, Qing Zhu, Shihui Sun, Chang Liu, Xinrong Tao, Chien-Te K. Tseng, Stanley Perlman, Shibo Jiang (), Yusen Zhou () and Fang Li ()
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Lanying Du: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center
Wanbo Tai: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center
Yang Yang: University of Minnesota Medical School
Guangyu Zhao: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Qing Zhu: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Shihui Sun: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Chang Liu: University of Minnesota Medical School
Xinrong Tao: University of Texas Medical Branch
Chien-Te K. Tseng: University of Texas Medical Branch
Stanley Perlman: University of Iowa
Shibo Jiang: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center
Yusen Zhou: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Fang Li: University of Minnesota Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms13473

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