Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 haemagglutinin against lethal H5N1 influenza.
BACKGROUND
Recent outbreaks of highly pathogenic H5N1 viruses in humans indicate that no endogenous protection exists in the general population. Vaccination programmes against this new pathogen require synthesis of endogenous antibodies and cannot provide any immediate protection in the event of a pandemic. Passive immunization with humanized neutralizing monoclonal antibodies can prove to be promising in preventing a catastrophic pandemic.


METHODS
A murine monoclonal antibody (mAb) 3B1 of immunoglobulin M isotype was switched to a chimeric immunoglobulin G1. BALB/c mice were used to study the protective efficacy of the chimeric mAbs against a lethal H5N1 virus challenge with strains from clades 1 and 2.1. Kinetics of the viral load were determined during the course of the treatment.


RESULTS
The chimeric mAb, in passive administration, was able to protect 100% of the mice when challenged with H5N1 strains from clades 1 or 2.1. Prophylaxis at 1 day prior to challenge and treatment at 1 day after challenge with this mAb resulted in the clearance of the virus from the lungs of the infected mice within 6 days post-viral challenge.


CONCLUSIONS
Passive immunotherapy using chimeric mAb 3B1 can be an effective tool in both the prophylaxis and treatment of highly pathogenic H5N1 infection, providing the immediate immunity needed to contain a future influenza pandemic.
Prabhu
Nayana
N
Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore.
Prabakaran
Mookkan
M
Hongliang
Qian
Q
He
Fang
F
Ho
Hui-Ting
HT
Qiang
Jia
J
Goutama
Michael
M
Lim
Angeline Pei-Chiew
AP
Hanson
Brendon J
BJ
Kwang
Jimmy
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000628:therapy*; D011292:Premedication; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007155:Immunologic Factors; D011993:Recombinant Fusion Proteins; C109963:hemagglutinin, avian influenza A virus