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Respir Res. 2006 Oct 14;7:126.

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

Author information

1
Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore 117510. hbrendon@dso.org.sg

Abstract

BACKGROUND:

Highly 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.

METHODS:

Neutralizing 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.

RESULTS:

Two 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.

CONCLUSION:

Prophylaxis 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.

PMID:
17040574
PMCID:
PMC1626464
DOI:
10.1186/1465-9921-7-126
[Indexed for MEDLINE]
Free PMC Article
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