4ZPT

Structure of MERS-Coronavirus Spike Receptor-binding Domain (England1 Strain) in Complex with Vaccine-Elicited Murine Neutralizing Antibody D12 (Crystal Form 1)

Summary for 4ZPT

• Entry DOI: 10.2210/pdb4zpt/pdb
• Related: 4KR0 4ZPV 4ZPW
• Descriptor: D12 Fab Heavy chain, D12 Fab Light chain, Spike glycoprotein, ... (5 entities in total)
• Functional Keywords: vaccine, immunogen, viral protein-immune system complex, viral protein/immune system
• Biological source: Human coronavirus EMC (isolate United Kingdom/H123990006/2012) (HCoV-EMC); More
• Cellular location: Spike protein S2: Virion membrane ; Single-pass type I membrane protein . Spike protein S1: Virion membrane ; Peripheral membrane protein : K9N5Q8
• Total number of polymer chains: 6
• Total formula weight: 140092.24

Authors

Joyce, M.G.,Mascola, J.R.,Graham, B.S.,Kwong, P.D. (deposition date: 2015-05-08, release date: 2015-10-21, Last modification date: 2020-07-29)

Primary citation

Joyce, M.G.
Evaluation of candidate vaccine approaches for MERS-CoV
Nat Commun, 6:7712-, 2015

PubMed Abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

PubMed: 26218507
DOI: 10.1038/ncomms8712

Experimental method

X-RAY DIFFRACTION (2.591 Å)