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Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters - PubMed

  • ️Sun Jan 01 2006

. 2006 Mar 1;193(5):685-92.

doi: 10.1086/500143. Epub 2006 Jan 27.

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Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters

Anjeanette Roberts et al. J Infect Dis. 2006.

Abstract

Background: Immunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and for the treatment of cancers and autoimmune diseases. MAb 201 is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific MAb that prevents establishment of viral replication in vitro and prevents viral replication in vivo when administered prophylactically. The efficacy of MAb 201 in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model that supports SARS-CoV replication to high levels and displays severe pathological changes associated with infection, including pneumonitis and pulmonary consolidation.

Methods: Golden Syrian hamsters that were intranasally inoculated with SARS-CoV were treated with various doses of MAb 201 or an irrelevant MAb 24 h after inoculation. Two to 7 days after infection, the hamsters were killed, and their lungs were collected for evaluation of viral titers and pathological findings.

Results: Postexposure treatment with MAb 201 can alleviate the viral burden and associated pathological findings in a golden Syrian hamster model of SARS-CoV infection. After a hamster is treated with MAb 201, its viral burden is reduced by 102.4-103.9 50% tissue-culture infectious doses per gram of tissue, and the severity of associated pathological findings, including interstitial pneumonitis and consolidation, is also remarkably reduced.

Conclusions: The demonstration of successful postexposure MAb 201 therapy in an animal model that demonstrates viral replication and associated pulmonary pathological findings suggests that MAb 201 may be useful in the arsenal of tools to combat SARS.

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Figures

Table 1
Table 1

Viral titers in lungs obtained from hamsters treated with monoclonal antibody 201 (MAb 201) after challenge with severe acute respiratory syndrome–associated coronavirus (SARS-CoV)

Table 2
Table 2

Findings of histopathological evaluations of lungs obtained from hamsters treated with monoclonal antibody 201 (MAb 201) after challenge with severe acute respiratory syndrome–associated coronavirus (SARS-CoV)

Figure 1
Figure 1

Hematoxylin-eosin staining of formalin-fixed hamster lungs after severe acute respiratory syndrome–associated coronavirus infection and antibody treatment. A–C Differences in the severity of interstitial pneumonitis: mild (A) moderate (B) and severe (C). D–F Differences in the severity of consolidation: mild (D) moderate (E) and severe (F). G Photomicrograph of a normal hamster lung with no interstitial pneumonitis or consolidation. Original magnification, ×25

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