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A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

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Sucharitha Balu, Rajko Reljic, Melanie J. Lewis, Richard J. Pleass, Richard McIntosh, Cees van Kooten, Marjolein van Egmond, Stephen Challacombe, Jenny M. Woof, Juraj Ivanyi

Original languageEnglish
Pages (from-to)3113-3119
Number of pages7
JournalJournal of Immunology
Volume186
Issue number5
DOIs
Accepted/In press14 Dec 2010
Published1 Mar 2011

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Abstract

Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties of a novel human IgA1, constructed using a single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified Ab monomer revealed high binding affinities for the mycobacterial alpha-crystallin Ag and for the human Fc alpha RI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 and recombinant mouse IFN-gamma significantly inhibited pulmonary H37Rv infection in mice transgenic for human CD89 but not in CD89-negative littermate controls, suggesting that binding to CD89 was necessary for the IgA-imparted passive protection. 2E9IgA1 added to human whole-blood or monocyte cultures inhibited luciferase-tagged H37Rv infection although not for all tested blood donors. Inhibition by 2E9IgA1 was synergistic with human rIFN-gamma in cultures of purified human monocytes but not in whole-blood cultures. The demonstration of the mandatory role of Fc alpha RI (CD89) for human IgA-mediated protection is important for understanding of the mechanisms involved and also for translation of this approach toward development of passive immunotherapy of tuberculosis. The Journal of Immunology, 2011, 186: 3113-3119.

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