Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.
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.
Wang
Xiliang
X
Department of Immunology, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.
Ni
Bing
B
Du
Xinan
X
Zhao
Guangyu
G
Gao
Wenda
W
Shi
Xinfu
X
Zhang
Songle
S
Zhang
Liangyan
L
Wang
Dong
D
Luo
Deyan
D
Xing
Li
L
Jiang
Haiyan
H
Li
Wanling
W
Jiang
Man
M
Mao
Liwei
L
He
Yangdong
Y
Xiao
Yu
Y
Wu
Yuzhang
Y
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000918:Antibody Specificity; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses; D007116:Immunization, Passive; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D051379:Mice; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000628:therapy*; D014709:Vero Cells
D000914:Antibodies, Viral; D007140:Immunoglobulin Fab Fragments