๐ 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
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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
keywords
๐ severe acute (1373)
๐ serum samples (106)
๐ present study (186)
๐ spike protein (353)
๐ cleavage site (85)
๐ infectious disease (312)
๐ host cell (262)
๐ respiratory syndrome (2004)
๐ results suggest (206)
๐ acute respiratory (1734)
๐ infectious diseases (94)
author
๐ค Miyoshi-Akiyama, Tohru
๐ค Ishida, Isao
๐ค Fukushi, Masaya
๐ค Yamaguchi, Keina
๐ค Matsuoka, Yusuke
๐ค Ishihara, Takashi
๐ค Tsukahara, Masayoshi
๐ค Hatakeyama, Seisuke
๐ค Itoh, Norikazu
๐ค Morisawa, Aki
๐ค Yoshinaka, Yoshiyuki
๐ค Yamamoto, Naoki
๐ค Lianfeng, Zhang
๐ค Chuan, Qin
๐ค Kirikae, Teruo
๐ค Sasazuki, Takehiko
year
โฐ 2011
issn
๐ 00221899
volume
203
number
11
page
1574-1581
citedbycount
11
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