Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.

Abstract

The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.

• Authors: Xiliang Wang, Bing Ni, Xinan Du, Guangyu Zhao, Wenda Gao, Xinfu Shi, Songle Zhang, Liangyan Zhang, Dong Wang, Deyan Luo, Li Xing, Haiyan Jiang, Wanling Li, Man Jiang, Liwei Mao, Yangdong He, Yu Xiao, Yuzhang Wu
• Journal: Antiviral therapy (Antivir Ther) Vol. 10 Issue 5 Pg. 681-90 ( 2005) ISSN: 1359-6535 [Print] England
• PMID: 16152762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Immunoglobulin Fab Fragments

Topics

• Animals
• Antibodies, Viral (immunology, pharmacology, therapeutic use, toxicity)
• Antibody Specificity
• Chlorocebus aethiops
• Cytopathogenic Effect, Viral (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Horses
• Immunization, Passive
• Immunoglobulin Fab Fragments (administration & dosage, immunology, therapeutic use, toxicity)
• Injections, Intraperitoneal
• Mice
• Neutralization Tests
• Severe acute respiratory syndrome-related coronavirus (immunology)
• Severe Acute Respiratory Syndrome (immunology, therapy)
• Vero Cells