Research Papers:
Protective cellular immunity generated by cross-presenting recombinant overlapping peptide proteins
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Abstract
Lili Cai1,*, Jianbo Zhang2,*, Renying Zhu1, Weixing Shi1, Xiaobing Xia1, Mark Edwards3, William Finch3, Anthony Coombs3, Ju Gao2, Kangwen Chen2, Sophie Owen5, Shisong Jiang1,3,4,5 and Wenshu Lu1,4
1Oxford Vacmedix (Changzhou) Company Ltd, Changzhou, Jiangsu, China
2The No.2 People’s Hospital of Dali, Dali, Yunnan, China
3Oxford Vacmedix UK Limited, Oxford, United Kingdom
4Shanghai JW Inflinhix Co Ltd, Shanghai, China
5Department of Oncology, University of Oxford, Oxford, United Kingdom
*These authors contributed equally to this work
Correspondence to:
Wenshu Lu, email: [email protected]
Shisong Jiang, email: [email protected]
Keywords: vaccines, peptide immunization, overlapping peptide, antigen processing, cross-presentation
Received: June 14, 2017 Accepted: August 14, 2017 Published: August 24, 2017
ABSTRACT
Priming of naive CD8+ and CD4+ T cells by dendritic cells (DCs) requires effective antigen presentation on both MHC class I and II molecules. We have developed a novel technology to use recombinant overlapping peptides (ROP) that stimulate both CD8+ and CD4+ T cell immune responses. The single chain protein of a ROP is made up of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, a protease found in the endosomes of DCs. We designed synthetic genes encoding ROPs derived from ovalbumin (OVA), tuberculosis protein (CFP10-ESAT6), human papilloma virus (HPV) protein (E7) and survivin, a protein commonly over-expressed in tumour cells. An epitope from ROP-OVA was cross-presented and detected by a CD8+ T cell receptor-like antibody (TCR like Ab). Human DCs pulsed with ROP-survivin activated CD8+ T cells. CD4-low PBMCs from HIV and TB co-infected patients recognized ROP-CFP10-ESAT6 compared to a soluble form of the antigen. Immunization of mice with ROP-survivin or ROP-HPV-E7 generated specific cellular immune responses and protected mice from inoculation with melanoma B16 cells expressing survivin or HPV-E7 proteins. Together these data provide evidence to support ROP as a central component of a new platform for therapeutic vaccines and diagnostics.
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PII: 20407