An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza A antibodies.
Cell Host Microbe
; 14(1): 93-103, 2013 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-23870317
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Plasmócitos
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Testes de Neutralização
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Influenza Humana
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Anticorpos Antivirais
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Host Microbe
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos