Cross presentation of antigens of recombinant overlapping peptides to optimise vaccines against tumour and infectious diseases

Nominating Supervisor: Shisong Jiang

Second Supervisor:  Nicola Burgess Brown

The Project

We have developed a technology to producing overlapping peptides - bacterial expression of an amino acid sequence corresponding to overlapping peptide sequences spanning the length of a protein of interest interspersed with enzymatic cleavage sites. The recombinant product can then be broken down by the cleavage sites for enzymes present in human antigen presenting cells to have a therapeutic effect. The overlapping peptides made that way are called recombinant overlapping peptides (ROPs).

This technology has applications in vaccine and diagnosis development. For vaccines, it can be used alone or in combination with other therapies to treat a wide range of human cancers or infectious diseases. The technology can also be used in diagnosis to assess T cell immunity which is important for monitoring and controlling cancer and microbial infections. The ROP technology platform has a number of distinct advantages over existing methods of activating or monitoring cellular immunity.

A DPhil student is required to explore the technology further to look for possibilities to enhance antigen presentation in both antigen presenting cells and target cells. This will be done through developing one or two candidates of vaccines to preclinical stage.

The Training

The DPhil student will be trained to learn in-depth on antigen presentation and cross-presentation. He/she will learn a wide spectrum of technologies from biochemistry (protein expression and purification) to immuno-assays (antigen presentation, T cell measurement etc). He/she will also carry out collaborative research with other academic and industrial institutions.

Publications

Cai, L., Zhang, J., Zhu, R., Shi, W., Xia, X., Edwards, M., . . . Lu, W. (2017). Protective cellular immunity generated by cross-presenting recombinant overlapping peptide proteins. Oncotarget, 8(44), 76516-76524. doi:10.18632/oncotarget.20407

Tchilian, E., Ahuja, D., Hey, A., Beverley, P., & Jiang, S. (2013). Immunization with different formulations of Mycobacterium tuberculosis antigen 85A induces immune responses with different specificity and protective efficacy. Vaccine. doi:10.1016/j.vaccine.2013.07.040

Zhang, H., Hong, H., Li, D., Ma, S., Di, Y., Stoten, A., . . . Jiang, S. (2009). Comparing pooled peptides with intact protein for accessing cross-presentation pathways for protective CD8+and CD4+T cells. Journal of Biological Chemistry, 284(14), 9184-9191. doi:10.1074/jbc.M809456200