title: Protein coated microcrystals formulated with model antigens and modified with calcium phosphate exhibit enhanced phagocytosis and immunogenicity.
abstract: Protein-coated microcrystals (PCMCs) were investigated as potential vaccine formulations for a range of model antigens. Presentation of antigens as PCMCs increased the antigen-specific IgG responses for all antigens tested, compared to soluble antigens. When compared to conventional aluminium-adjuvanted formulations, PCMCs modified with calcium phosphate (CaP) showed enhanced antigen-specific IgG responses and a decreased antigen-specific IgG1:IgG2a ratio, indicating the induction of a more balanced Th1/Th2 response. The rate of antigen release from CaP PCMCs, in vitro, decreased strongly with increasing CaP loading but their immunogenicity in vivo was not significantly different, suggesting the adjuvanticity was not due to a depot effect. Notably, it was found that CaP modification enhanced the phagocytosis of fluorescent antigen-PCMC particles by J774.2 murine monocyte/macrophage cells compared to soluble antigen or soluble PCMCs. Thus, CaP PCMCs may provide an alternative to conventional aluminium-based acellular vaccines to provide a more balanced Th1/Th2 immune response.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. Electronic address: sjones@biooutsource.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jones
authors.affiliation: Division of Bacteriology, National Institute of Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK. Electronic address: Cathy.Asokanathan@nibsc.hpa.org.uk.
authors.forename: Catpagavalli
authors.initials: C
authors.lastname: Asokanathan
authors.affiliation: Division of Bacteriology, National Institute of Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK. Electronic address: Dorota.Kmiec@nibsc.hpa.org.uk.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kmiec
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. Electronic address: June.Irvine@glasgow.ac.uk.
authors.forename: June
authors.initials: J
authors.lastname: Irvine
authors.affiliation: Division of Cellular Biology and Imaging, National Institute of Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK. Electronic address: Roland.Fleck@nibsc.hpa.org.uk.
authors.forename: Roland
authors.initials: R
authors.lastname: Fleck
authors.affiliation: Division of Bacteriology, National Institute of Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK. Electronic address: Dorothy.Xing@nibsc.hpa.org.uk.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Xing
authors.affiliation: Department of P&A Chemistry, WestChem, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK; XstalBio Ltd., CIDS, Thomson Building, University Avenue, Glasgow G12 8QQ, UK. Electronic address: b.d.moore@strath.ac.uk.
authors.forename: Barry
authors.initials: B
authors.lastname: Moore
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. Electronic address: Roger.Parton@glasgow.ac.uk.
authors.forename: Roger
authors.initials: R
authors.lastname: Parton
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. Electronic address: John.Coote@glasgow.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Coote
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D002130:Calcium Phosphates; D007074:Immunoglobulin G; C020243:calcium phosphate
keywords: Adjuvant; Calcium phosphate; Microparticles; Phagocytosis