title: A Nanoparticle Based Sp17 Peptide Vaccine Exposes New Immuno-Dominant and Species Cross-reactive B Cell Epitopes.
abstract: Sperm protein antigen 17 (Sp17), expressed in primary as well as in metastatic lesions in >83% of patients with ovarian cancer, is a promising ovarian cancer vaccine candidate. Herein we describe the formulation of nanoparticle based vaccines based on human Sp17 (hSp17) sequence derived peptides, and map the immuno-dominant T cell and antibody epitopes induced using such formulations. The primary T and B cell immuno-dominant region within Sp17 was found to be the same when using biocompatible nanoparticle carriers or the conventional "mix-in" pro-inflammatory adjuvant CpG, both mapping to amino acids (aa) 111-142. However, delivery of hSp17111-142 as a nanoparticle conjugate promoted a number of new properties, changing the dominant antibody isotype induced from IgG2a to IgG1 and the fine specificity of the B cell epitopes within hSp17111-142, from an immuno-dominant region 134-142 aa for CpG, to region 121-138 aa for nanoparticles. Associated with this change in specificity was a substantial increase in antibody cross-reactivity between mouse and human Sp17. These results indicate conjugation of antigen to nanoparticles can have major effects on fine antigen specificity, which surprisingly could be beneficially used to increase the cross-reactivity of antibody responses.
authors.affiliation: Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia. Sue.Xiang@monash.edu.|Therapeutics and Regenerative Medicine Division, The Monash Institute of Medical Engineering (MIME), Monash University, Clayton, VIC 3800, Australia. Sue.Xiang@monash.edu.
authors.forename: Sue D
authors.initials: SD
authors.lastname: Xiang
authors.affiliation: Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia. qgao10@student.monash.edu.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia. Kirsty.Wilson@monash.edu.
authors.forename: Kirsty L
authors.initials: KL
authors.lastname: Wilson
authors.affiliation: PX Biosolutions Pty Ltd, PO Box 290, South Melbourne, VIC 3205, Australia. Arne.Heyerick@pxbiosolutions.com.
authors.forename: Arne
authors.initials: A
authors.lastname: Heyerick
authors.affiliation: Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia. Magdalena.Plebanski@monash.edu.|Therapeutics and Regenerative Medicine Division, The Monash Institute of Medical Engineering (MIME), Monash University, Clayton, VIC 3800, Australia. Magdalena.Plebanski@monash.edu.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
keywords: Sp17; antibody; cancer; cross-reactivity; immunodomunant; nanoparticles; ovarian; testis-antigen; vaccine