Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen

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Abstract
Significance: Coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) cause severe respiratory distress with high fatality rates. The spike (S) glycoprotein is a determinant of host range and is the target of neutralizing antibodies and subunit vaccine development. We describe an engineering strategy for stabilization of soluble S proteins in the prefusion conformation, which results in greatly increased expression, conformational homogeneity, and elicitation of potent antibody responses. Cryo-EM structures of the stabilized MERS-CoV S protein in complex with a stem-directed neutralizing antibody provide a molecular basis for host-cell protease requirements and identify a site of immune pressure. We also defined four conformational states of the trimer wherein each receptor-binding domain is either packed together at the membrane-distal apex or rotated into a receptor-accessible conformation.
Funding Information
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (R01AI127521)
  • HHS | NIH | National Institute of General Medical Sciences (P20GM113132)
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (AI005125)