title: Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans.
abstract: Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
authors: Shuai
authors: S
authors: Dong
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
authors: Hongxi
authors: H
authors: Shi
authors: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun City, Jilin Province, 130021 P. R. China.
authors: Donghui
authors: D
authors: Cao
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
authors: Yicun
authors: Y
authors: Wang
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
authors: Xintong
authors: X
authors: Zhang
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
authors: Yan
authors: Y
authors: Li
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.|Key Laboratory of Molecular Epigenetics of MOE, Changchun City, Jilin Province, 130024 P. R. China.
authors: Xiang
authors: X
authors: Gao
authors: Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
authors: Li
authors: L
authors: Wang
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000276:immunology; D017104:Bacteriophage M13; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008807:Mice, Inbred BALB C; D061905:Single-Domain Antibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D002721:omega-Chloroacetophenone
chemical_list: D000908:Antibodies, Fungal; D005656:Fungal Proteins; D061905:Single-Domain Antibodies; D002721:omega-Chloroacetophenone; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida