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A novel human IgA monoclonal antibody protects against tuberculosis.

Balu, Sucharitha, Reljic, Rajko, Lewis, Melanie J., Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296, McIntosh, Richard, van Kooten, Cees, van Egmond, Marjolein, Challacombe, Stephen, Woof, Jenny M and Ivanyi, Juraj (2011) 'A novel human IgA monoclonal antibody protects against tuberculosis.'. The Journal of Immunology, Vol 186, Issue 5, pp. 3113-3119.

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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 α-crystallin Ag and for the human FcαRI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 and recombinant mouse IFN-γ 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-γ in cultures of purified human monocytes but not in whole-blood cultures. The demonstration of the mandatory role of FcαRI (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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance.
WF Respiratory System > Tuberculosis > WF 250 Immunological aspects
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.4049/​jimmunol.1003189
Related URLs:
Depositing User: Mary Creegan
Date Deposited: 17 Jun 2011 15:47
Last Modified: 06 Feb 2018 13:03
URI: http://archive.lstmed.ac.uk/id/eprint/2039

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