A multivalent vaccine and single platform diagnostic for bacterial respiratory diseases of pigs

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine


Pigs can get many diseases but amongst the most serious are those caused by bacteria that can live in their throats, airways or tonsils but can also cause severe lung (or brain) infections. Large numbers of animals may die quickly (acute infection) or fail to grow normally (chronic infection). Such infections cost the world's pig industry huge sums of money each year. A major problem is that such infections are difficult to diagnose. Some strains of a particular bacterium cause disease and others do not and there is no reliable method to distinguish them. Most experts agree that the best way to control the spread of bacteria is to use a vaccine. However, current vaccines are poor. They do not prevent the spread of bacteria from animal to animal and only work against a few strains. We plan to target four of the most common bacteria that cause infections in pigs: Actinobacillus pleuropneumoniae, Haemophilus parasuis, Mycoplasma hyopneumoniae and Streptococcus suis. The last of these can also cause serious disease in humans such as blood poisoning (septicaemia) and brain infection (meningitis) especially in people who work with pigs. Our aim is to develop (1) tests that can tell which strains can cause disease or not and (2) a single vaccine that protects against more than one of the pig pathogens. We will isolate bacteria from UK pigs and, using genetic techniques, find out how many different sorts of each bacterium are present. The results will be used to develop a diagnostic test and also help in choosing appropriate vaccine candidates. The work will be done in collaboration with partners in the Veterinary Laboratories Agency, Scottish Agricultural College, Agri-Food and Biosciences Institute and Huazhong Agricultural University (Wuhan, China). A successful conclusion to the project (diagnostics and vaccines) will prevent animal suffering (through reduction in infections via vaccination, early diagnosis and treatment, prevention of unnecessary treatment) and save the pig industry substantial amounts of money contributing to the prosperity of the UK.

Technical Summary

The worldwide economic/welfare burden resulting from bacterial respiratory diseases of pigs is enormous. Control of infection is hampered by the lack of efficacious vaccines and diagnostic tools. Problems include differentiating low/non-virulent/pathogenic strains and the incomplete correlation of phenotype to pathogenic potential. Traditional vaccines (bacterins) typically only protect against homologous strains and do not prevent colonisation. This research program concerns 4 major bacterial respiratory pathogens of pigs: A. pleuropneumoniae, H. parasuis, M. hyopneumoniae and S. suis. All cause substantial mortality and morbidity in pigs worldwide. Additionally S. suis causes severe outbreaks of human infection. There is an international imperative for improved diagnostics and vaccines for all these pathogens. Now is the opportunity to exploit genome data and technical innovations, many of which have been pioneered by the applicants. A multi-centre integrated approach will be used to develop a multivalent vaccine and single platform diagnostic for the 4 bacteria. The largest known collection of disease/non-disease associated UK isolates will be assembled and subjected to MLST and comparative phylogenetics (genomotyping). The data will be used to develop a genotypic based diagnostic. Genetic tools will be developed that allow mutagenesis and/or heterologous antigen expression. Functional genomic screens and follow up studies will identify live attenuated vaccine (LAVs) candidates and conserved immunogenic proteins. The latter will be used as the basis for protein array-based diagnostics and be heterologously expressed either in LAVs or vaccines based on protein glycan coupling technology. The multivalent vaccine and single platform diagnostics will be evaluated in experimental and field trials in collaboration with UK /Chinese veterinarians. The major deliverable will be to reduce animal suffering and the economic and welfare burden of disease in the pig industry.


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Description We have developed new genetic tools for four pig pathogens, and through gene analysis of those pathogens identified prospective vaccine and diagnostic candidates. The work has led to the development of tests for three of the pathogens that are used by veterinary diagnostic laboratories. As added value, a number of papers have been published detailing the extent of antimicrobial resistance in the UK for three of the pathogens.
Exploitation Route Vaccines and diagnostics through industrial partners.
Sectors Agriculture, Food and Drink,Healthcare

Description The diagnostic tests we have developed have been applied to clinical samples submitted by veterinary practices to enable disease diagnosis.
First Year Of Impact 2016
Sector Agriculture, Food and Drink
Impact Types Economic

Title Multiplex PCR for identification of fve bacterial lung pathogens of pigs 
Description The multiplex PCR detects Actinobacillus pleuropneumoniae, Haemophilus parasuis, Pasteurella multocida, Streptococcus suis, and Mycoplasma hyopneumoniae. The genes targeted are either published (P. multocida) or unique (as found in the LoLa award). It can be used on pig lung, joint, tonsil, brain, oral fluids, and saliva. 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? No  
Impact The mPCR in combination with a novel point of care device (already developed at Imperial) formed the basis of a successful BBSRC response mode application to detect 8 pathogens of the porcine respiratory disease complex. Extensive use with samples in collbaoration with Ceva led to that company supporting the PERP-ID application. We are in early discussions with Chinese Partners (through a BBSRC China Partnering Award) to develop a kit using the mPCR for use in the Chinese marketplace. Gene sequences cannot be patented, so the most likely route for IP protection is through copyrighting. 
Title Plasmids that allow transposon mutagenesis in Actinobacillus pleuropneumoniae and related bacteria 
Description Plasmids that allow transposon mutagenesis in Actinobacillus pleuropneumoniae and related bacteria such as Haemophlus influenzae, Mannheimia haemolytica, Aggregatibacter actinomycetemcomitans and Pasteurella multocida. The mutagenesis system uses the mariner transposon that inserts all around the chromosome. The system has been designed to be compatible with new generation sequencing. Its use allows the identification of essential genes in the bacteria of interest. Such genes are potential targets for new antibiotics. 
Type Of Material Biological samples 
Year Produced 2018 
Provided To Others? Yes  
Impact We have supplied transposon mutant libraries to researchers at harwell (UK) and Harvard (USA) wh 
Description Ceva collab 
Organisation Ceva Animal Health
Country United Kingdom 
Sector Private 
PI Contribution Diagnostic development
Collaborator Contribution Provision of clinical samples
Impact None
Start Year 2016
Description Hungary collab 
Organisation University of Veterinary Medicine Budapest
Country Hungary 
Sector Academic/University 
PI Contribution Whole genome sequence data
Collaborator Contribution Immunological serotyping
Impact One paper describing a new serotype of the pig pathogen Actinobacillus pleuropneumoniae
Start Year 2015
Description Zoetis collab 
Organisation Zoetis
Country United States 
Sector Private 
PI Contribution Translational Research.
Collaborator Contribution Financial contribution to the research.
Impact Novel diagnostic tests and vaccines.
Start Year 2011