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A pan-H1 anti-hemagglutinin monoclonal antibody with potent broad-spectrum efficacy in vivo

tetano

Editor, Senior Moderator
J Virol. 2012 Apr 4. [Epub ahead of print]
A pan-H1 anti-hemagglutinin monoclonal antibody with potent broad-spectrum efficacy in vivo.
Tan GS, Krammer F, Eggink D, Kongchanagul A, Moran TM, Palese P.
Source

Department of Microbiology, Mount Sinai School of Medicine, New York City, New York, 10029.
Abstract

Seasonal epidemics caused by antigenic variations in influenza A virus remain a public health concern and an economic burden. The isolation and characterization of broadly neutralizing anti-hemagglutinin monoclonal antibodies (mAb) have highlighted the presence of highly conserved epitopes in divergent influenza A viruses. Here, we describe the generation and characterization of a mouse monoclonal antibody designed to target the conserved regions of the hemagglutinin of influenza A H1 viruses, a subtype, which has caused pandemics in the human population in both the 20(th) and 21(st) century. By sequentially immunizing mice with plasmid DNA encoding the hemagglutinin of antigenically different H1 influenza A viruses (A/South Carolina/1/1918, A/USSR/92/1977 and A/California/4/2009), we isolated and identified mAb 6F12. Similar to other broadly neutralizing mAb previously described, mAb 6F12 has no hemagglutination inhibition activity against influenza A viruses and targets the stalk region of hemagglutinins. As designed, it has neutralizing activity against a divergent panel of H1 viruses in vitro, representing 79 years of antigenic drift. Most notably, mAb 6F12 prevented gross weight loss against divergent H1 viruses in passive transfer experiments in mice, both in pre- and post-exposure prophylaxis regimens. The broad, but specific activity of mAb 6F12 highlights the potent efficacy of monoclonal antibodies directed against a single subtype of influenza A virus.

PMID:
22491456
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22491456
 
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