title: Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses.
abstract: BACKGROUND
  Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.
  
  
  METHODS
  Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.
  
  
  RESULTS
  Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.
  
  
  CONCLUSIONS
  Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.
authors.affiliation: Department of Epidemiology.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Agnihothram
authors.forename: Robin
authors.initials: R
authors.lastname: Gopal
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Yount
authors.forename: Eric F
authors.initials: EF
authors.lastname: Donaldson
authors.forename: Vineet D
authors.initials: VD
authors.lastname: Menachery
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Graham
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Scobey
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Gralinski
authors.forename: Mark R
authors.initials: MR
authors.lastname: Denison
authors.forename: Maria
authors.initials: M
authors.lastname: Zambon
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D015153:Blotting, Western; D002685:Chiroptera; D003332:Coronaviridae / Q000276:immunology* / Q000302:isolation & purification; D000086462:Coronavirus Nucleocapsid Proteins; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000086462:Coronavirus Nucleocapsid Proteins; D019590:Nucleocapsid Proteins; D064370:Spike Glycoprotein, Coronavirus
keywords: Diagnostics; MERS-CoV Vaccine Design; Serology; Synthetic Genomics