TY - JOUR
T1 - A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis
AU - Balu, Sucharitha
AU - Reljic, Rajko
AU - Lewis, Melanie J.
AU - Pleass, Richard J.
AU - McIntosh, Richard
AU - van Kooten, Cees
AU - van Egmond, Marjolein
AU - Challacombe, Stephen
AU - Woof, Jenny M.
AU - Ivanyi, Juraj
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
U2 - 10.4049/jimmunol.1003189
DO - 10.4049/jimmunol.1003189
M3 - Article
SN - 1550-6606
VL - 186
SP - 3113
EP - 3119
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -
