TOWARDS PASSIVE IMMUNOTHERAPY OF PANDEMIC INFLUENZA

Abstract

THE PERSISTENT EVOLUTION AND CIRCULATION OF HIGHLY PATHOGENIC AVIAN INFLUENZA H5N1 VIRUSES POSES A SERIOUS THREAT TO GLOBAL HEATH AND HAMPERS PANDEMIC PREPAREDNESS THROUGH CONVENTIONAL VACCINE STRATEGIES. COMBINATION PASSIVE IMMUNOTHERAPY USING NON-COMPETING NEUTRALIZING ANTIBODIES HAS BEEN PROPOSED AS A VIABLE ALTERNATIVE TO PROVIDE BROAD PROTECTION AGAINST DRIFT VARIANTS. THIS APPROACH NECESSITATES THE PRE-PANDEMIC PRODUCTION AND CHARACTERIZATION OF POTENTLY NEUTRALIZING MONOCLONAL ANTIBODIES (MABS). THIS STUDY CHARACTERIZES TWO SUCH MABS, 9F4 AND 4F3, WHICH WERE SELECTED BASED ON THEIR ABILITY TO BROADLY NEUTRALIZE MULTIPLE H5N1 CLADE VIRUSES. 9F4 WAS FOUND TO BE A HOMOSUBTYPIC MAB WHILE 4F3 CROSS-NEUTRALIZES H7 HA BELONGING TO THE EURASIAN LINEAGE. 9F4 WAS CONVERTED FROM IGG2B TO MOUSE-HUMAN CHIMERIC IGG1 AND IGA1. THESE CHIMERIC MABS WERE FOUND TO RETAIN VARYING DEGREES OF BINDING AND NEUTRALIZING ACTIVITY AGAINST H5N1. THE EPITOPE MAPPING OF 9F4 WAS EXTENDED AND COMPARED TO OTHER