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A novel human IgA monoclonal antibody protects against tuberculosis

A novel human IgA monoclonal antibody protects against tuberculosis

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Authors

  • 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 (Lead / Corresponding author)

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Info

Original languageEnglish
Pages3113-3119
Number of pages7
JournalJournal of Immunology
Journal publication date1 Mar 2011
Volume186
Issue5
DOIs
StatePublished
Peer-reviewedYes

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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