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Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model.

AbstractBACKGROUND:
There is still no effective method to prevent or treat severe acute respiratory syndrome (SARS), which is caused by SARS coronavirus (CoV). In the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing SARS-CoV in vitro in a Rhesus macaque model of SARS.
METHODS:
The antibody 5H10 was obtained by vaccination of KM mice bearing human immunoglobulin genes with Escherichia coli-producing recombinant peptide containing the dominant epitope of the viral spike protein found in convalescent serum samples from patients with SARS.
RESULTS:
5H10, which recognized the same epitope that is also a cleavage site critical for the entry of SARS-CoV into host cells, inhibited propagation of the virus and pathological changes found in Rhesus macaques infected with the virus through the nasal route. In addition, we analyzed the mode of action of 5H10, and the results suggested that 5H10 inhibited fusion between the virus envelope and host cell membrane. 5H10 has potential for use in prevention and treatment of SARS if it reemerges.
CONCLUSIONS:
This study represents a platform to produce fully human antibodies against emerging infectious diseases in a timely and safe manner.
AuthorsTohru Miyoshi-Akiyama, Isao Ishida, Masaya Fukushi, Keina Yamaguchi, Yusuke Matsuoka, Takashi Ishihara, Masayoshi Tsukahara, Seisuke Hatakeyama, Norikazu Itoh, Aki Morisawa, Yoshiyuki Yoshinaka, Naoki Yamamoto, Zhang Lianfeng, Qin Chuan, Teruo Kirikae, Takehiko Sasazuki
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 203 Issue 11 Pg. 1574-81 (Jun 01 2011) ISSN: 1537-6613 [Electronic] United States
PMID21592986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
Topics
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Animals, Genetically Modified
  • Antibodies, Monoclonal (immunology, metabolism, pharmacology)
  • Antibodies, Neutralizing (immunology, metabolism)
  • Antibodies, Viral (immunology, metabolism)
  • Blotting, Western
  • Catalytic Domain
  • Cell Fusion
  • Disease Models, Animal
  • Giant Cells (drug effects)
  • Humans
  • Immunohistochemistry
  • Lung (pathology, virology)
  • Macaca mulatta
  • Membrane Glycoproteins (genetics, immunology)
  • Mice
  • Peptidyl-Dipeptidase A
  • Recombinant Proteins (genetics, immunology, pharmacology)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severe acute respiratory syndrome-related coronavirus (immunology)
  • Severe Acute Respiratory Syndrome (immunology, therapy, virology)
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins (genetics, immunology)

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