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

Autor: Ten Feizi, Lars P. Erwig, Sosthene Essono, Rodrigo Belmonte, Hillary Workman, Lisete M. Silva, Angelina S. Palma, Fiona M. Rudkin, Allan Jensen, Elizabeth M. Johnson, Ingrida Raziunaite, Donna M. MacCallum, Neil A. R. Gow
Přispěvatelé: UCIBIO - Applied Molecular Biosciences Unit, DQ - Departamento de Química
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Nature Communications, Vol 9, Iss 1, Pp 1-16 (2018)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Rudkin, F, 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, vol. 9, no. 1, 5288 (2018) . https://doi.org/10.1038/s41467-018-07738-1
ISSN: 2041-1723
Popis: FCT Investigator IF/00033/2012. Wellcome Trust (086827, 075470, 099215, 099197 and 101873) 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). Wellcome Trust grant 099197MA . 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. publishersversion published
Databáze: OpenAIRE