Human single-chain antibodies that neutralize homologous and heterologous strains and clades of influenza A virus subtype H5N1.
BACKGROUND
Human antibodies that interfere with the biological activity of haemagglutinins (HAs) of influenza viruses have high potential as an antiviral agent.


METHODS
Human single-chain antibody fragments (HuScFv) to recombinant and native HAs of the influenza virus H5N1 subtype were produced using a human antibody phage display library with the intention to increase the therapeutic arsenal against this highly pathogenic virus.


RESULTS
The HuScFv inhibited HA activity and neutralized infectivity of both homologous and heterologous strains and clades of the H5N1 subtype in Madin-Darby canine kidney cell cultures. Intraperitoneally injected HuScFv also mediated immunotherapeutic protection in mice that were intranasally challenged with highly pathogenic H5N1 viruses belonging to different strains and clades.


CONCLUSIONS
Our data indicate that it might be worth pursuing these HuScFv further for future consideration as candidates for influenza intervention and treatment.
Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Santi
S
Maneewatch
Jeeraphong
J
Thanongsaksrikul
Thaweesak
T
Songserm
Kanyarat
K
Thueng-In
Kasem
K
Kulkeaw
Umaporn
U
Thathaisong
Potjanee
P
Srimanote
Pongsri
P
Tongtawe
Pramuan
P
Tapchaisri
Wanpen
W
Chaicumpa
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000008:administration & dosage*; D002460:Cell Line; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007128:Immunoglobulin Fragments / Q000008:administration & dosage; D007155:Immunologic Factors / Q000008:administration & dosage; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology; D007251:Influenza, Human / Q000628:therapy*; D007274:Injections, Intraperitoneal; D051379:Mice
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007128:Immunoglobulin Fragments; D007155:Immunologic Factors