Journal Article

Mapping T and B cell epitopes in sperm protein 17 to support the development of an ovarian cancer vaccine

Gao, Qian, Plebanski, Magdalena, Wilson, Kirsty L., Heyerick, Arne, Xiang, Sue D.

2015

Overview

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-2Kb 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants, Immunologic - administration & dosage / Allergy and Immunology / Animal models / animal ovaries / Animals / antibodies / Antibodies - blood / Antibody / Antigens / Antigens, Surface - immunology / B cell epitopes / B-Lymphocytes - immunology / Cancer therapies / Cancer Vaccines - administration & dosage / Cancer Vaccines - immunology / Cancer Vaccines - isolation & purification / Carrier Proteins - immunology / CD4-positive T-lymphocytes / CD8 epitopes / CD8-positive T-lymphocytes / death / Design / Enzyme-Linked Immunosorbent Assay / Enzyme-Linked Immunospot Assay / Epitope Mapping / epitopes / Epitopes, B-Lymphocyte - immunology / Epitopes, T-Lymphocyte - immunology / Female / Humans / immune response / Immunization / Immunogenicity / Immunotherapy / interferon-gamma / Interferon-gamma - secretion / interleukin-4 / Lymphocytes / metastasis / mice / Mice, Inbred C57BL / Mice, SCID / Mice, Transgenic / Oligodeoxyribonucleotides - administration & dosage / Ovarian cancer / ovarian neoplasms / Ovarian Neoplasms - therapy / Overlapping peptides / patients / Peptides / Proteins / Sperm / Sperm protein 17 (Sp17) / surface proteins / T-Lymphocytes - immunology / toxicity / transgenic animals / Tumors / Vaccine / Vaccines / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - immunology / Vaccines, Synthetic - isolation & purification / women / Womens health