An EBV vaccine to prevent cancers and MS?

Project Overview

Most humans are infected with Epstein-Barr virus. The virus has the ability to establish latency in B cells and pre-malignant epithelial cells, and, via expression of viral oncogenes, is responsible for c. 120,000 cases of cancer each year. Less well-known is the existence of evidence linking EBV to a number of auto-immune diseases, including the observation that multiple sclerosis (MS) is exceptionally rare in individuals uninfected with EBV. It has thus been suggested that most cases of MS could be prevented by an effective EBV vaccine.

This project would seek to develop such a vaccine, based upon the induction of antibodies against viral glycoproteins essential for cell entry. The student would design recombinant protein antigens, characterise their ability to induce neutralising antibody after vaccination of mice, and assess their ability to protect against EBV in vivo (using ‘humanised’ mice bearing human cells susceptible to infection). We would also seek to identify and characterise mouse and human monoclonal antibodies against the critical viral glycoprotein ‘gB’, which is required for virus-cell membrane fusion. Polyclonal antibody against gB is known to neutralise the virus, but at present there is little understanding of the antibody-sensitive epitopes or the protein’s pre-fusion structure, and hence poor understanding of how to produce an optimal gB vaccine antigen.

The ubiquity of EBV in human populations offers outstanding opportunities for small and yet informative clinical trials and experimental medicine. The project would be truly translational, and a core aim would be rapid progression of the tools developed towards human studies.

Training Opportunities

Dr Douglas & Prof Draper aim to offer high-quality supervision and allow them to make the most of the opportunities afforded by an Oxford DPhil, working within a stimulating, supportive and enjoyable environment. Prospective applicants are encouraged to contact Sandy (sandy.douglas@ndm.ox.ac.uk) for further information and/or to be put in touch with current lab members.

All students are expected to present their research internally and at relevant conferences, and to work towards publications. A student pursuing this project could expect to learn a broad range of transferable practical techniques in molecular biology, virology, and immunology.

The Jenner Institute is Europe’s largest academic translational vaccinology research centre, with activity extending from basic microbiological and immunological research into first-time-in-human clinical trials and subsequent international field trials. The Institute’s close integration of pre-clinical and clinical activities offers near-unique opportunities for students to be involved throughout this process. With other active programmes within the Institute targeting diseases including HIV, TB, dengue, cancer and influenza, DPhil students have the opportunity to interact with senior researchers with a wide variety of expertise, and to develop a broad skill-set to support a career in 21st century translational medicine.

Theme

Immunology & Infectious Disease

Admissions

Project reference number: 1075

Funding and admissions information

Supervisors

Name Department Institution Country Email
Sandy Douglas Jenner Institute Oxford University, Henry Wellcome Building for Molecular Physiology GBR sandy.douglas@ndm.ox.ac.uk
Simon Draper Jenner Institute Oxford University, Old Road Campus Research Building GBR simon.draper@ndm.ox.ac.uk

There are no publications listed for this DPhil project.