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Original article

Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 haemagglutinin against lethal H5N1 influenza

Nayana Prabhu, Mookkan Prabakaran, Qian Hongliang, Fang He, Hui-Ting Ho, Jia Qiang, Michael Goutama, Angeline Pei-Chiew Lim, Brendon J Hanson, Jimmy Kwang

Corresponding author name: Jimmy Kwang
Corresponding author e-mail: kwang@tll.org.sg

Citation: Antiviral Therapy 2009; 14:911-921
doi: 10.3851/IMP1413

Date accepted: 07 June 2009
Date published online: 11 November 2009

Abstract

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.

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