Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice

Brendon J Hanson,Adrianus Cm Boon,Eng Eong Ooi,Angeline Pc Lim,Ashley Webb,Richard J Webby

doi:10.1186/1465-9921-7-126

Brendon J Hanson, Adrianus Cm Boon + Show 4 more

Open Access

https://doi.org/10.1186/1465-9921-7-126

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Abstract

BackgroundHighly pathogenic avian H5N1 influenza virus is a major public health concern. Given the lack of effective vaccine and recent evidence of antiviral drug resistance in some isolates, alternative strategies for containment of a possible future pandemic are needed. Humanized monoclonal antibodies (mAbs) that neutralize H5N1 virus could be used as prophylaxis and treatment to aid in the containment of such a pandemic.MethodsNeutralizing mAbs against H5 hemagglutinin were humanized and introduced into C57BL/6 mice (1, 5, or 10 mg/kg bodyweight) one day prior to-, one day post- and three days post-lethal challenge with H5N1 A/Vietnam/1203/04 virus. Efficacy was determined by observation of weight loss as well as survival.ResultsTwo mAbs neutralizing for antigenically variant H5N1 viruses, A/Vietnam/1203/04 and A/Hong Kong/213/03 were identified and humanized without loss of specificity. Both antibodies exhibited prophylactic efficacy in mice, however, VN04-2-huG1 performed better requiring only 1 mg/kg bodyweight for complete protection. When used to treat infection VN04-2-huG1 was also completely protective, even when introduced three days post infection, although higher dose of antibody was required.ConclusionProphylaxis and treatment using neutralizing humanized mAbs is efficacious against lethal challenge with A/Vietnam/1203/04, providing proof of principle for the use of passive antibody therapy as a containment option in the event of pandemic influenza.

Highlights

Pathogenic avian H5N1 influenza virus is a major public health concern
The protective efficacy of neutralizing humanized monoclonal antibodies specific for the hemagglutinin of a Z-genotype influenza A H5N1 virus in mice when used as prophylaxis before, and treatment following-lethal challenge with fully pathogenic H5N1 virus
Characterization of H5 neutralizing monoclonal antibodies (mAbs) Monoclonal antibodies against H5N1 viruses of the Z genotype which had shown high titers in hemagglutinin inhibition (HI) tests against their respective immunogens were tested for their virus neutralizing capabilities

Summary

Introduction

Pathogenic avian H5N1 influenza virus is a major public health concern. Given the lack of effective vaccine and recent evidence of antiviral drug resistance in some isolates, alternative strategies for containment of a possible future pandemic are needed. While the current data does not deter stockpiling of oseltamivir for pandemic response [15], it does suggest that alternative strategies for prophylaxis or treatment are warranted Since this time, the H5N1 influenza epidemic of the Asian bird population has continued. The increased incidence of human infection, coupled with evidence of expanding host range and widespread distribution of H5N1 viruses has heightened concern that acquisition of the properties necessary, through mutation or genetic reassortment, for human-to-human transmission is only a matter of time Should this occur, humans would have virtually no immunity to such novel viruses which may result in a human influenza pandemic of potentially catastrophic proportions [7]

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