combination therapy using chimeric monoclonal antibodies protects mice from lethal h5n1 infection and prevents formation of escape mutants联合治疗使用嵌合单克隆抗体保护小鼠免受致命的h5n1感染和防止逃避突变体的形成.pdfVIP

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combination therapy using chimeric monoclonal antibodies protects mice from lethal h5n1 infection and prevents formation of escape mutants联合治疗使用嵌合单克隆抗体保护小鼠免受致命的h5n1感染和防止逃避突变体的形成.pdf

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combination therapy using chimeric monoclonal antibodies protects mice from lethal h5n1 infection and prevents formation of escape mutants联合治疗使用嵌合单克隆抗体保护小鼠免受致命的h5n1感染和防止逃避突变体的形成

Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants 1. 1. 1 1 1 1 Mookkan Prabakaran , Nayana Prabhu , Fang He , Qian Hongliang , Hui-Ting Ho , Jia Qiang , Tao 1 2 1,3 Meng , Michael Goutama , Jimmy Kwang * 1 Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore, 2 Tridel Biosciences International Pte Ltd, Singapore, Singapore, 3 Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore, Singapore Abstract Background: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. Methods/Principal Findings: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses