Author(s):
Rudkin, Fiona M. ; Raziunaite, Ingrida ; Workman, Hillary ; Essono, Sosthene ; Belmonte, Rodrigo ; MacCallum, Donna M. ; Johnson, Elizabeth M. ; Silva, Lisete M. ; Palma, Angelina S. ; Feizi, Ten ; Jensen, Allan ; Erwig, Lars P. ; Gow, Neil A.R.
Date: 2018
Persistent ID: http://hdl.handle.net/10362/127783
Origin: Repositório Institucional da UNL
Project/scholarship:
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-QUI%2F112537%2F2009/PT;
Subject(s): Chemistry(all); Biochemistry, Genetics and Molecular Biology(all); Physics and Astronomy(all); SDG 3 - Good Health and Well-being
Description
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.
