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Multivalent poultry vaccine development using Protein Glycan Coupling Technology.

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dc.contributor.authorMauri, Marta
dc.contributor.authorSannasiddappa, Thippeswamy H
dc.contributor.authorVohra, Prerna
dc.contributor.authorCorona-Torres, Ricardo
dc.contributor.authorSmith, Alexander A
dc.contributor.authorChintoan-Uta, Cosmin
dc.contributor.authorBremner, Abi
dc.contributor.authorTerra, Vanessa S
dc.contributor.authorAbouelhadid, Sherif
dc.contributor.authorStevens, Mark P
dc.contributor.authorGrant, Andrew J
dc.contributor.authorCuccui, Jon
dc.contributor.authorWren, Brendan W
dc.contributor.orcidMauri, Marta [0000-0003-0098-3900]
dc.contributor.orcidChintoan-Uta, Cosmin [0000-0003-1841-7819]
dc.date.accessioned2021-11-04T01:48:31Z
dc.date.available2021-11-04T01:48:31Z
dc.date.issued2021-10-02
dc.date.updated2021-11-04T01:48:30Z
dc.description.abstract<h4>Background</h4>Poultry is the world's most popular animal-based food and global production has tripled in the past 20 years alone. Low-cost vaccines that can be combined to protect poultry against multiple infections are a current global imperative. Glycoconjugate vaccines, which consist of an immunogenic protein covalently coupled to glycan antigens of the targeted pathogen, have a proven track record in human vaccinology, but have yet to be used for livestock due to prohibitively high manufacturing costs. To overcome this, we use Protein Glycan Coupling Technology (PGCT), which enables the production of glycoconjugates in bacterial cells at considerably reduced costs, to generate a candidate glycan-based live vaccine intended to simultaneously protect against Campylobacter jejuni, avian pathogenic Escherichia coli (APEC) and Clostridium perfringens. Campylobacter is the most common cause of food poisoning, whereas colibacillosis and necrotic enteritis are widespread and devastating infectious diseases in poultry.<h4>Results</h4>We demonstrate the functional transfer of C. jejuni protein glycosylation (pgl) locus into the genome of APEC χ7122 serotype O78:H9. The integration caused mild attenuation of the χ7122 strain following oral inoculation of chickens without impairing its ability to colonise the respiratory tract. We exploit the χ7122 pgl integrant as bacterial vectors delivering a glycoprotein decorated with the C. jejuni heptasaccharide glycan antigen. To this end we engineered χ7122 pgl to express glycosylated NetB toxoid from C. perfringens and tested its ability to reduce caecal colonisation of chickens by C. jejuni and protect against intra-air sac challenge with the homologous APEC strain.<h4>Conclusions</h4>We generated a candidate glycan-based multivalent live vaccine with the potential to induce protection against key avian and zoonotic pathogens (C. jejuni, APEC, C. perfringens). The live vaccine failed to significantly reduce Campylobacter colonisation under the conditions tested but was protective against homologous APEC challenge. Nevertheless, we present a strategy towards the production of low-cost "live-attenuated multivalent vaccine factories" with the ability to express glycoconjugates in poultry.
dc.identifier.doi10.17863/CAM.77713
dc.identifier.issn1475-2859
dc.identifier.otherPMC8487346
dc.identifier.other34600535
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330272
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1475-2859
dc.sourcenlmid: 101139812
dc.subjectPoultry
dc.subjectVaccine
dc.subjectCampylobacter jejuni
dc.subjectGlycoconjugates
dc.subjectGlycoengineering
dc.subjectAPEC
dc.subjectOne Health
dc.subjectNetb
dc.subjectLive-attenuated
dc.subjectPgct
dc.titleMultivalent poultry vaccine development using Protein Glycan Coupling Technology.
dc.typeArticle
prism.issueIdentifier1
prism.publicationNameMicrobial cell factories
prism.volume20
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P013740/1, BB/N001591/1)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1186/s12934-021-01682-4

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