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Exploring the early response to (para)typhoid exposure in a human challenge model of infection

Student name: Amber Barton

Supervisors: Professor Andrew Pollard, Dr Jennifer Hill and Dr Irina Mohorianu

Description: Several plasma cytokines have been found to transiently increase around 12 hours after healthy volunteers are experimentally exposed to Salmonella Typhi, regardless of whether they go on to develop signs of infection. This raises a number of questions, including the identity and location of the cells producing these cytokines, whether we can detect other immunological signatures of exposure, and whether such signatures differ between those who become infected and those who remain well. In this project these questions are being addressed using whole blood transcriptional analysis. Early differences in the transcriptome between individuals who remain well and those who develop disease have indicated genes which might be involved in protection.  Furthermore, gene set enrichment analysis of blood transcriptional changes occurring 12 h post-exposure has allowed characterisation of early cellular responses, the significance of which is being investigated further with in vitro experiments.

Source of funding: St Cross Paediatrics Scholarship (Department of Paediatrics and St Cross College), with project support from Wellcome Trust and the Bill and Melinda Gates Foundation.

Further information:

Blohmke, C. et al. (2016) Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever. Journal of Experimental Medicine.

 

Evaluating the effect of immunisation with capsular group B meningococcal vaccines on meningococcal carriage

Student name:  Jeremy Carr

Supervisors:  Dr Matthew Snape; Professor Martin Maiden

Description:  Capsular group B meningococcal (MenB) vaccines provide direct protection against invasive MenB disease, however the effect on herd protection is not known. This study will evaluate the influence of MenB immunisation on oropharyngeal carriage in teenagers, and consequently the potential for these vaccines to disrupt transmission and provide broad community protection against MenB disease. Given the potential for immunisation with the subcapsular protein antigens in MenB vaccines to impact on the carriage of non-MenB pathogenic and commensal Neisseria species, carriage rates of these organisms will also be evaluated. Understanding the influence of MenB protein-based vaccines on herd protection will inform current vaccine policy and future vaccine development.

Source of funding:  University of Oxford; Clarendon Scholarship; National Institute for Health Research; Department of Health.  

Further information:  https://beontheteam.web.ox.ac.uk/

 

Assessing the immune mechanisms underlying the immunogenicity to meningococcal group B vaccines

Student nameDylan Sheerin

Supervisors: Prof. Andrew Pollard, Dr Christina Dold, Dr Christine Rollier

Description: The Gram-negative bacterium Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD), a severe bacterial infection which occurs predominantly in infants within the first years of life. Two meningococcus group B (MenB) vaccines have been licensed, but both have significant drawbacks. A novel MenB vaccine has been developed at the Oxford Vaccine Group, based on a viral vector. The vaccine candidate induced strong and persistent protective immune responses in mice after a single dose, and a phase I trial to assess its safety and immunogenicity in healthy adults is ongoing. The D.Phil student is working on understanding the mechanisms which underlie the responses induced by these distinct vaccines at the genetic, cellular and systems level, and the results will contribute to the rational design of future vaccine candidates for MenB and other bacterial diseases. 

Source of funding: Medical Research Council

Further information: Currently in second year.

 

RaPaed-TB: Evaluation of New Diagnostics in Childhood TB

 

Student name: Laura Olbrich

Supervisor: Professor Andrew Pollard; Dr. Rinn Song

Description: Globally, children account for an estimated one million TB cases and more then 200,000 deaths due to TB per year. The main challenge is adequate and timely diagnosis as currently available diagnostic tests fail to diagnose the majority of children with TB. New testing strategies are therefore urgently needed. In a prospective, multi-country clinical study in four African countries and in India, diagnostic performance data on a number of promising novel assays and sampling strategies will be generated. In addition, the study will derive diagnostic and screening algorithms for TB using existing and these novel tests.

Source of funding: EDCTP