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An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies

tetano

Editor, Senior Moderator
Cell Host Microbe. 2013 Jul 17;14(1):93-103. doi: 10.1016/j.chom.2013.06.004.
An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies.
Nakamura G, Chai N, Park S, Chiang N, Lin Z, Chiu H, Fong R, Yan D, Kim J, Zhang J, Lee WP, Estevez A, Coons M, Xu M, Lupardus P, Balazs M, Swem LR.
Source

Antibody Engineering Department, Genentech, South San Francisco, CA 94080.
Abstract

Recent advances enabling the cloning of human immunoglobulin G genes have proven effective for discovering monoclonal antibodies with therapeutic potential. However, these antibody-discovery methods are often arduous and identify only a few candidates from numerous antibody-secreting plasma cells or plasmablasts. We describe an in vivo enrichment technique that identifies broadly neutralizing human antibodies with high frequency. For this technique, human peripheral blood mononuclear cells from vaccinated donors are activated and enriched in an antigen-specific manner for the production of numerous antigen-specific plasmablasts. Using this technology, we identified four broadly neutralizing influenza A antibodies by screening only 840 human antibodies. Two of these antibodies neutralize every influenza A human isolate tested and perform better than the current anti-influenza A therapeutic, oseltamivir, in treating severe influenza infection in mice and ferrets. Furthermore, these antibodies elicit robust in vivo synergism when combined with oseltamivir, thus highlighting treatment strategies that could benefit influenza-infected patients.

Copyright ? 2013 Elsevier Inc. All rights reserved.

PMID:
23870317
[PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/23870317
 
Re: An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies

Cell Host Microbe. 2013 Jul 17;14(1):7-8. doi: 10.1016/j.chom.2013.07.002.
Greasing the SCIDs for Universal Flu Antibodies.
Yewdell JW, Ince WL.
Source

Laboratory of Viral Diseases, NIAID, Bethesda, MD 20892, USA. Electronic address: jyewdell@nih.gov.
Abstract

In this issue, Nakamura et al. (2013) describe a robust SCID mouse-based method for isolating human monoclonal antibodies of desired specificity from adoptively transferred human B cells. As proof of principle, they isolate human mAbs that could potentially be used to treat or prevent human infection with any influenza A virus strain.

Copyright ? 2013 Elsevier Inc. All rights reserved.

PMID:
23870308
[PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/23870308
 
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