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


CONCLUSIONS
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.
Hanson
Brendon J
BJ
Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore 117510. hbrendon@dso.org.sg
Boon
Adrianus C M
AC
Lim
Angeline P C
AP
Webb
Ashley
A
Ooi
Eng Eong
EE
Webby
Richard J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D053124:Influenza A Virus, H5N1 Subtype; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins