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

Tohru 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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. 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.

Original languageEnglish
Pages (from-to)1574-1581
Number of pages8
JournalJournal of Infectious Diseases
Volume203
Issue number11
DOIs
Publication statusPublished - Jun 1 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

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