Development and characterisation of neutralising mouse-human chimeric anti-SARS-CoV monoclonal antibodies

Introduction. Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) is the etiological agent behind a pandemic in 2002/2003 that caused ∼8000 infections with a 10% case-fatality rate. The health community reacted quickly to contain the pandemic, and no further outbreaks of the disease have been recorded. However, no vaccine is currently available and treatment options are limited in the event another outbreak occurs. Passive immunity via neutralizing monoclonal antibodies would provide a unique and immediate treatment option.; Methods. Using recombinant DNA technology, the variable regions of four anti-SARS-CoV monoclonal antibodies (mAb) of the F26 series were inserted into the pIGG expression vector and transiently expressed in 293T cells. The resulting chimerics were purified and characterised by immunochemical and immunobiological assays. The parental mouse mAbs were characterised in parallel, and the results compared.; Results. ELISA and Western Blotting on parental and chimeric F26 series mAbs demonstrate that the antibodies bind the ACE2 receptor-binding domain of the SARS-spike glycoprotein. The binding characteristics are maintained between the chimeric and parental mAbs. F26G18 (murine) and 18H18L (chimeric) neutralise the in vitro infectivity of the TOR2 strain of SARS-CoV with identical titres (0.31 and 0.37 mug/mL respectively) in the same assay system.; Conclusions. A series of neutralising chimeric antibodies specific for SARS-CoV have been developed using recombinant DNA technology. In particular, the chimeric 18H18L retains the high neutralising titre of the parental version, giving it the potential to be used therapeutically in the event of a SARS outbreak.