Analysing the phase variable genes of Campylobacter jejuni - tools for novel diagnostics and vaccines

Lead Research Organisation: University of Leicester
Department Name: Genetics


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Description The University of Leicester, through research led by Dr Chris Bayliss, has developed expertise and know how around identification of phase variation diversity in Campylobacter jejuni (C. jejuni) bacteria. The team have characterised phase-variable antigens which can facilitate survival of C. jejuni in chickens and could be viable vaccine targets for poultry. The University of Leicester knowhow and methodologies developed to analyse potential early stage vaccines in preclinical/clinical
development, could be utilised by those working on R&D in the space.

The secondary and primary market research conducted by IPP in compiling this report has indicated that the C. jejuni vaccine research space is dominated by academic institutions, both universities and government funded. These are predominantly US based, with the UK a close second and Canada, the Netherlands, France and Germany also key publishers in C. jejuni research. The report lists many of these organisations in the sections that follow. Of note is the US Navy Research Centre which is undergoing phase II clinical trial for a capsid based virus like particle vaccine. Indeed a search for
ongoing and past clinical trials for a C. jejuni vaccine has indicated that the only promising candidate in clinical development is the US Navy conjugate capsule based vaccine. IPP have made contact with TechLink, a consultancy company assisting with the commercial mapping of the technology in the US and they have confirmed the difficulties in identifying potential commercial partners for this type of technology. The commercial companies identified to have worked previously in the C. jejuni vaccine space have largely been dissolved or acquired by larger pharmaceutical companies (GSK, Merck,

The market analysis carried out for this report indicates there is a large and unmet market for C. jejuni vaccine and treatment solutions. Epidemiological figures vary but illness due to campylobacter is estimated to affect 9 million Europeans annually, with strains C. jejuni and C.coli estimated to account for 90% of all cases. Furthermore food safety studies have found a prevalence of C. jejuni in chicken carcasses amounting to 75.8% in some cases. Historically there have been many vaccine and treatment development failures, particularly during the 1990s, and the pathogen is a notoriously difficult target. For this reason IPP suggest that the phase variation expertise would be useful to those developing solutions to target C. jejuni infection, however IPP secondary and primary research indicates that currently commercial companies may not have C. jejuni in the forefront of their
research agendas. Primary feedback from Merck (MSD Animal Health), the second largest animal health company by sales volume, was however positive and the company is open to discussions in future about how they can work with Leicester to best utilise this expertise for their candidate development process. Similarly feedback from Zoetis, the largest animal health company globally, who have a programme in the area and would be interested to see further in vivo work. However
this positive feedback has not been overwhelming across the animal health industry, with companies such as Boehringer Ingelheim declining further interest and there was a lack of response to IPP's approaches made to Hipra (the latter have previously indicated interest in Campylobacter affecting

This report has also examined the C. jejuni diagnostics market, also a large and important market for food safety. There are many solutions currently available, both traditional culture based assays and next generation genomic and proteomic tools to detect the bacteria in food samples. The detection current methods focus on distinguishing different species of microorganism in food (salmonella, campylobacter, listeria) and increasingly, different strains within the sample. Technology focus is on rapid, improved accuracy and portable diagnostics. As such the provision of methods to detect phase variation using Leicester expertise is unlikely to provide added value to this market.

The Leicester expertise can therefore be useful to a select number of animal health companies which have research teams working on C. jejuni. A selection of these companies has been referenced in this report. The larger opportunity may be collaboration with other academic and government
funded institutions, of which there are many globally, with a focus on C. jejuni research. Several of these organisations are listed throughout this report. For both the human and animal health sector applications, the feedback we have received indicates the importance of having in vivo data before the companies will engage with the Leicester team. Fortunately the team has in vivo work underway and the results. Once the in vivo data is known we recommend following up again with the
animal health companies and in particular Zoetis and MSD Animal Health. In parallel to this we also recommend that the upcoming CHRO Campylobacter conference in New Zealand in November 2015 is used to further highlight the technology and used as a forum to have meetings with those companies that are also attending.
Exploitation Route We have recently obtained funding for a post-doctoral research who will be able to make contact with commercial companies and explore some proof-in-principle research to highlight the potential utility of our research. We will contact companies and researchers that were established at the CHRO2015 meeting in New Zealand and through the report from IPP. We have followed up contacts with VaxAlta, a small start-up company interested in Campylobacter vaccines, and analysed phase-variable genes in some of their samples. The data from VaxAlta was published in Applied and Environmental Microbiology in an article that provides a proof-in-principle of how our technological expertise can be used in understanding commercially-relevant data outputs, this article showed that phase variation was not contributing to evasion of vaccine-elicited protective responses.
Sectors Agriculture, Food and Drink,Healthcare

Description Through this award we commissioned a company called IP Pragmatics to make contacts with companies within the poultry research sector. The remit was to ascertain the interest in our methodologies and expertise for analysing hypermutable sequences of the foodborne pathogen Campylobacter jejuni. We engaged with members of IP Pragmatics to prepare suitable information sources - word documents and powerpoint presentations - for circulation to a range of potential interested parties. The company then performed a series of literature searches to identify potential partners and engaged with their own previously established contacts. IP Pragmatics then provided us with a report on their findings and made recommendations about current views on our expertise. They also made recommendations and provided contact details that could be used for future exploration of potential commercial partners.
First Year Of Impact 2015
Sector Agriculture, Food and Drink
Impact Types Economic

Description REF Impact Fund
Amount £8,155 (GBP)
Organisation University of Leicester 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 07/2016
Description Analysis of phase variable genes of Campylobacter jejuni strain 81-176 
Organisation VaxAlta Inc.
Country Canada 
Sector Private 
PI Contribution Developed an assay for a specific strain of Campylobacter jejuni and tested whether changes in phase-variable genes contributed to the ability of this strain to avoid vaccine elicited immune responses.
Collaborator Contribution Provision of samples.
Impact One publication in Applied and Environmental Microbiology and another manuscript submitted.
Start Year 2016