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 μg of the F(ab’)₂ fragments could completely neutralize 1x10⁴ 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.