A novel human IgA monoclonal antibody protects against tuberculosis

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.

KW - FC-ALPHA-RI

KW - MYCOBACTERIUM-TUBERCULOSIS

KW - PASSIVE IGA

KW - POSTCHEMOTHERAPY RELAPSE

KW - MEDIATED IMMUNITY

KW - SURFACE-ANTIGEN

KW - SERUM THERAPY

KW - INFECTION

KW - MICE

KW - RECEPTOR

UR - https://www.scopus.com/pages/publications/79952759532

U2 - 10.4049/jimmunol.1003189

DO - 10.4049/jimmunol.1003189

M3 - Article

C2 - 21257971

SN - 0022-1767

VL - 186

SP - 3113

EP - 3119

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -