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

• Published in: Respiratory research 2006-10, Vol.7 (1), p.126-126, Article 126
• Main Authors: Hanson, Brendon J, Boon, Adrianus C M, Lim, Angeline P C, Webb, Ashley, Ooi, Eng Eong, Webby, Richard J
• Format: Article
• Language: English
• Subjects: AIDS vaccines; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antiviral agents; Avian influenza; Biopharmaceuticals; Drug resistance; Female; Health aspects; House mouse; Humans; Immunization, Passive - methods; Influenza A Virus, H5N1 Subtype; Influenza vaccines; Influenza virus; Influenza viruses; Lectins; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - therapy; Orthomyxoviridae Infections - virology; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-7-126

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. 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. 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. 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.