Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis

Fiona M Rudkin; Ingrida Raziunaite; Hillary Workman; Sosthene Essono; Rodrigo Belmonte; Donna M MacCallum; Elizabeth M Johnson; Lisete M Silva; Angelina S Palma; Ten Feizi; Allan Jensen; Lars P Erwig; Neil A. R. Gow

doi:10.1038/s41467-018-07738-1

Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis

Fiona M Rudkin, Ingrida Raziunaite, Hillary Workman, Sosthene Essono, Rodrigo Belmonte, Donna M MacCallum, Elizabeth M Johnson, Lisete M Silva, Angelina S Palma, Ten Feizi, Allan Jensen, Lars P Erwig, Neil A. R. Gow^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

9 Downloads (Pure)

Abstract

The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.

Original language	English
Article number	5288
Number of pages	16
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-07738-1
Publication status	Published - 11 Dec 2018

Bibliographical note

We thank the BBSRC, SULSA BioSKAPE and Pfizer Inc. for funding for a studentship for F.M.R. and the Wellcome Trust (086827, 075470, 099215, 099197 and 101873) and a Wellcome Trust ISSF award (105625), MRC CiC (MC_PC_14114) and MRC Centre for Medical Mycology and University of Aberdeen for funding and a Wellcome Trust Strategic Award (097377) and a Wellcome Trust grant 099197MA to T.F. and FCT Investigator IF/00033/2012 and PTDC/QUI-QUI/112537/2009 to A.S.P. We thank Ian Broadbent, Angus McDonald and Ron Gladue for constructive discussions; Chris Boston and Amanda Fitzgerald for advice on antibody expression and purification; Ed Lavallie and Wayne Stochaj for design and expression of the recombinant Hyr1; Louise Walker for high-pressure freezing of samples for TEM analysis; Jeanette Wagener for endotoxin testing of mAbs for in vivo experiments; Yan Liu of the Glycosciences laboratory for insight in the analysis with N-glycan array; Rebecca Hall and Mark Gresnigt for providing fungal strains; Andrew Limper and Theodore J. Kottom for providing Pneumocystis infected lung tissue extracts; David Williams for C. albicans mannoprotein; Christopher Thornton for A. fumigatus mannoprotein; Katie J. Doores for mAb PGT 128; and Gordon Brown for the murine Fc-Dectin-1. We are grateful to Lucinda Wight, Debbie Wilkinson and Kevin MacKenzie in the Microscopy and Histology Core Facility (Aberdeen University) and Raif Yuecel in the Iain Fraser Cytometry Centre (Aberdeen University) for their expert help with microscopy and cytometry experiments. We are also grateful to the staff at the University of Aberdeen Medical Research Facility for assistance with in vivo experiments and members of the Glycosciences Laboratory for their support of the Carbohydrate Microarray Facility.

18 January 2019 - Author Correction: Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis
F. M. Rudkin, I. Raziunaite, H. Workman, S. Essono, R. Belmonte, D. M. MacCallum, E. M. Johnson, L. Silva, A. S. Palma, T. Feizi, A. Jensen, L. P. Erwig & N. A. R. Gow
Nature Communicationsvolume 10, Article number: 394 (2019)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-018-07738-1Licence: CC BY

Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Final published version, 2.27 MBLicence: CC BY

Fiona Rudkin
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Research Fellow
Person: Academic Related - Research

Iain Fraser Cytometry Centre
Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)
Institute of Medical Sciences
Research Facilities: Facility
Microscopy and Histology
Debbie Wilkinson (Manager) & Gillian Milne (Manager)
Medical Sciences
Research Facilities: Facility

Cite this

Rudkin, F. M., Raziunaite, I., Workman, H., Essono, S., Belmonte, R., MacCallum, D. M., Johnson, E. M., Silva, L. M., Palma, A. S., Feizi, T., Jensen, A., Erwig, L. P., & Gow, N. A. R. (2018). Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nature Communications, 9, Article 5288. https://doi.org/10.1038/s41467-018-07738-1

Rudkin, FM, Raziunaite, I, Workman, H, Essono, S, Belmonte, R, MacCallum, DM, Johnson, EM, Silva, LM, Palma, AS, Feizi, T, Jensen, A, Erwig, LP & Gow, NAR 2018, 'Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis', Nature Communications, vol. 9, 5288. https://doi.org/10.1038/s41467-018-07738-1

@article{02fef690a9eb4a06b913e6ffbb88fb42,

title = "Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis",

abstract = "The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.",

author = "Rudkin, {Fiona M} and Ingrida Raziunaite and Hillary Workman and Sosthene Essono and Rodrigo Belmonte and MacCallum, {Donna M} and Johnson, {Elizabeth M} and Silva, {Lisete M} and Palma, {Angelina S} and Ten Feizi and Allan Jensen and Erwig, {Lars P} and Gow, {Neil A. R.}",

note = "We thank the BBSRC, SULSA BioSKAPE and Pfizer Inc. for funding for a studentship for F.M.R. and the Wellcome Trust (086827, 075470, 099215, 099197 and 101873) and a Wellcome Trust ISSF award (105625), MRC CiC (MC_PC_14114) and MRC Centre for Medical Mycology and University of Aberdeen for funding and a Wellcome Trust Strategic Award (097377) and a Wellcome Trust grant 099197MA to T.F. and FCT Investigator IF/00033/2012 and PTDC/QUI-QUI/112537/2009 to A.S.P. We thank Ian Broadbent, Angus McDonald and Ron Gladue for constructive discussions; Chris Boston and Amanda Fitzgerald for advice on antibody expression and purification; Ed Lavallie and Wayne Stochaj for design and expression of the recombinant Hyr1; Louise Walker for high-pressure freezing of samples for TEM analysis; Jeanette Wagener for endotoxin testing of mAbs for in vivo experiments; Yan Liu of the Glycosciences laboratory for insight in the analysis with N-glycan array; Rebecca Hall and Mark Gresnigt for providing fungal strains; Andrew Limper and Theodore J. Kottom for providing Pneumocystis infected lung tissue extracts; David Williams for C. albicans mannoprotein; Christopher Thornton for A. fumigatus mannoprotein; Katie J. Doores for mAb PGT 128; and Gordon Brown for the murine Fc-Dectin-1. We are grateful to Lucinda Wight, Debbie Wilkinson and Kevin MacKenzie in the Microscopy and Histology Core Facility (Aberdeen University) and Raif Yuecel in the Iain Fraser Cytometry Centre (Aberdeen University) for their expert help with microscopy and cytometry experiments. We are also grateful to the staff at the University of Aberdeen Medical Research Facility for assistance with in vivo experiments and members of the Glycosciences Laboratory for their support of the Carbohydrate Microarray Facility. 18 January 2019 - Author Correction: Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis F. M. Rudkin, I. Raziunaite, H. Workman, S. Essono, R. Belmonte, D. M. MacCallum, E. M. Johnson, L. Silva, A. S. Palma, T. Feizi, A. Jensen, L. P. Erwig & N. A. R. Gow Nature Communicationsvolume 10, Article number: 394 (2019) ",

year = "2018",

month = dec,

day = "11",

doi = "10.1038/s41467-018-07738-1",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis

AU - Rudkin, Fiona M

AU - Raziunaite, Ingrida

AU - Workman, Hillary

AU - Essono, Sosthene

AU - Belmonte, Rodrigo

AU - MacCallum, Donna M

AU - Johnson, Elizabeth M

AU - Silva, Lisete M

AU - Palma, Angelina S

AU - Feizi, Ten

AU - Jensen, Allan

AU - Erwig, Lars P

AU - Gow, Neil A. R.

N1 - We thank the BBSRC, SULSA BioSKAPE and Pfizer Inc. for funding for a studentship for F.M.R. and the Wellcome Trust (086827, 075470, 099215, 099197 and 101873) and a Wellcome Trust ISSF award (105625), MRC CiC (MC_PC_14114) and MRC Centre for Medical Mycology and University of Aberdeen for funding and a Wellcome Trust Strategic Award (097377) and a Wellcome Trust grant 099197MA to T.F. and FCT Investigator IF/00033/2012 and PTDC/QUI-QUI/112537/2009 to A.S.P. We thank Ian Broadbent, Angus McDonald and Ron Gladue for constructive discussions; Chris Boston and Amanda Fitzgerald for advice on antibody expression and purification; Ed Lavallie and Wayne Stochaj for design and expression of the recombinant Hyr1; Louise Walker for high-pressure freezing of samples for TEM analysis; Jeanette Wagener for endotoxin testing of mAbs for in vivo experiments; Yan Liu of the Glycosciences laboratory for insight in the analysis with N-glycan array; Rebecca Hall and Mark Gresnigt for providing fungal strains; Andrew Limper and Theodore J. Kottom for providing Pneumocystis infected lung tissue extracts; David Williams for C. albicans mannoprotein; Christopher Thornton for A. fumigatus mannoprotein; Katie J. Doores for mAb PGT 128; and Gordon Brown for the murine Fc-Dectin-1. We are grateful to Lucinda Wight, Debbie Wilkinson and Kevin MacKenzie in the Microscopy and Histology Core Facility (Aberdeen University) and Raif Yuecel in the Iain Fraser Cytometry Centre (Aberdeen University) for their expert help with microscopy and cytometry experiments. We are also grateful to the staff at the University of Aberdeen Medical Research Facility for assistance with in vivo experiments and members of the Glycosciences Laboratory for their support of the Carbohydrate Microarray Facility. 18 January 2019 - Author Correction: Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis F. M. Rudkin, I. Raziunaite, H. Workman, S. Essono, R. Belmonte, D. M. MacCallum, E. M. Johnson, L. Silva, A. S. Palma, T. Feizi, A. Jensen, L. P. Erwig & N. A. R. Gow Nature Communicationsvolume 10, Article number: 394 (2019)

PY - 2018/12/11

Y1 - 2018/12/11

N2 - The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.

AB - The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.

U2 - 10.1038/s41467-018-07738-1

DO - 10.1038/s41467-018-07738-1

M3 - Article

C2 - 30538246

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 5288

ER -

Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis

Abstract

Bibliographical note

UN SDGs

Access to Document

Fingerprint

Profiles

Fiona Rudkin

Equipment

Iain Fraser Cytometry Centre

Microscopy and Histology

Cite this