Journal article
Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines
Nature communications, Vol.7, 13473
11/22/2016
DOI: 10.1038/ncomms13473
PMCID: PMC5121417
PMID: 27874853
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.
Details
- Title: Subtitle
- Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines
- Creators
- Lanying Du - Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USAWanbo Tai - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaYang Yang - Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USAGuangyu Zhao - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaQing Zhu - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaShihui Sun - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaChang Liu - Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USAXinrong Tao - The University of Texas Medical Branch at GalvestonChien-Te K Tseng - The University of Texas Medical Branch at GalvestonStanley Perlman - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242, USAShibo Jiang - Shanghai Medical College of Fudan UniversityYusen Zhou - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaFang Li - Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.7, 13473
- DOI
- 10.1038/ncomms13473
- PMID
- 27874853
- PMCID
- PMC5121417
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- R01 AI110700 / NIAID NIH HHS R21 AI113206 / NIAID NIH HHS R01 AI089728 / NIAID NIH HHS R21 AI109094 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS U01 AI124260 / NIAID NIH HHS R01 AI098775 / NIAID NIH HHS
- Language
- English
- Date published
- 11/22/2016
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777477702771
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