title: Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines.
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.
authors.affiliation: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Wanbo
authors.initials: W
authors.lastname: Tai
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Chien-Te K
authors.initials: CK
authors.lastname: Tseng
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
authors.affiliation: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.|Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D018352:Coronavirus Infections / Q000517:prevention & control*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology*; D021122:Protein Subunits / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology* / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D021122:Protein Subunits; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D022223:Vaccines, Subunit; D014765:Viral Vaccines