Mapping T and B cell epitopes in sperm protein 17 to support the development of an ovarian cancer vaccine.
Ovarian cancer (OC) is the seventh most common cancer in women worldwide, and the leading cause of death from gynaecological malignancy. Immunotherapeutic strategies including cancer vaccines are considered less toxic and more specific than current treatments. Sperm surface protein (Sp17) is a protein aberrantly expressed in primary as well as in metastatic lesions in >83% of ovarian cancer patients. Vaccines based on the Sp17 protein are immunogenic and protective in animal models. To map the immunogenic regions and support the development of human Sp17 peptide based vaccines, we used 6 overlapping peptides of the human Sp17 sequence adjuvanted with CpG to immunise humanised HLA-A2.1 transgenic C57BL/6 mice, and assessed immunogenicity by ELISPOT and ELISA. No CD8 T cells were found to be induced to a comprehensive panel of 10 HLA-A2.1 or H-2K(b) binding predicted epitopes. However, one of the 6 peptides, hSp17111-142, induced high levels of antibodies and IFN-γ producing T cells (but not IL-17 or IL-4) both in C57BL/6 and in C57BL/6-HLA-A2.1 transgenic mice. C57BL/6 mice immunised with CpG adjuvanted hSp17111-142 significantly prolonged the life-span of the mice bearing the ovarian carcinoma ID8 cell line. We further mapped the immuno-dominant B and T cell epitope regions within hSp17111-142 using ELISPOT and competition ELISA. Herein, we report the identification of a single immuno-dominant B cell (134-142 aa) epitope and 2 T helper 1 (Th1) cell epitopes (111-124 aa and 124-138 aa). These result together support further exploration of hSp17111-142 peptide formulations as vaccines against ovarian cancer.
Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: Sue.Xiang@monash.edu.
Sue D
SD
Xiang
Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: qgao10@student.monash.edu.
Qian
Q
Gao
Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: Kirsty.Wilson@monash.edu.
Kirsty L
KL
Wilson
PX Biosolutions Pty Ltd, PO Box 290, South Melbourne 3205, VIC, Australia. Electronic address: Arne.Heyerick@pxbiosolutions.com.
Arne
A
Heyerick
Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: Magdalena.Plebanski@monash.edu.
Magdalena
M
Plebanski
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000097:blood; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002148:Calmodulin-Binding Proteins; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification*; D002352:Carrier Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008565:Membrane Proteins; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000954:Antigens, Surface; C408982:CPG-oligonucleotide; D002148:Calmodulin-Binding Proteins; D019496:Cancer Vaccines; D002352:Carrier Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C090172:SPA17 protein, human; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
Antibody; B cell epitopes; CD8 epitopes; Overlapping peptides; Sperm protein 17 (Sp17); Vaccine