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A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance

dc.contributor.authorBadamchi-Zadeh, Alexander
dc.contributor.authorMcKay, Paul F.
dc.contributor.authorKorber, Bette T.
dc.contributor.authorBarinaga, Guillermo
dc.contributor.authorWalters, Adam A.
dc.contributor.authorNunes, Alexandra
dc.contributor.authorGomes, João Paulo
dc.contributor.authorFollmann, Frank
dc.contributor.authorTregoning, John S.
dc.contributor.authorShattock, Robin J.
dc.date.accessioned2017-02-15T16:02:11Z
dc.date.available2017-02-15T16:02:11Z
dc.date.issued2016-04-28
dc.descriptionThe Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fimmu.2016.00162pt_PT
dc.description.abstractBACKGROUND: A vaccine for Chlamydia trachomatis is of urgent medical need. We explored bioinformatic approaches to generate an immunogen against C. trachomatis that would induce cross-serovar T-cell responses as (i) CD4(+) T cells have been shown in animal models and human studies to be important in chlamydial protection and (ii) antibody responses may be restrictive and serovar specific. METHODS: A consensus antigen based on over 1,500 major outer membrane protein (MOMP) sequences provided high epitope coverage against the most prevalent C. trachomatis strains in silico. Having designed the T-cell immunogen, we assessed it for immunogenicity in prime-boost regimens. This consensus MOMP transgene was delivered using plasmid DNA, Human Adenovirus 5 (HuAd5) or modified vaccinia Ankara (MVA) vectors with or without MF59(®) adjuvanted recombinant MOMP protein. RESULTS: Different regimens induced distinct immune profiles. The DNA-HuAd5-MVA-Protein vaccine regimen induced a cellular response with a Th1-biased serum antibody response, alongside high serum and vaginal MOMP-specific antibodies. This regimen significantly enhanced clearance against intravaginal C. trachomatis serovar D infection in both BALB/c and B6C3F1 mouse strains. This enhanced clearance was shown to be CD4(+) T-cell dependent. Future studies will need to confirm the specificity and precise mechanisms of protection. CONCLUSION: A C. trachomatis vaccine needs to induce a robust cellular response with broad cross-serovar coverage and a heterologous prime-boost regimen may be an approach to achieve this.pt_PT
dc.description.sponsorshipAB was funded by the Wellcome Trust. RS was supported by the European Community’s European 7th Framework Program ADITEC (HEALTH-F4-2011-18 280873).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Immunol. 2016 Apr 28;7:162. doi: 10.3389/fimmu.2016.00162. eCollection 2016pt_PT
dc.identifier.doi10.3389/fimmu.2016.00162pt_PT
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/10400.18/4184
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationAdvanced Immunization Technologies
dc.relation.publisherversionhttp://journal.frontiersin.org/article/10.3389/fimmu.2016.00162/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectChlamydia Trachomatispt_PT
dc.subjectVaccinept_PT
dc.subjectDNA Vaccinespt_PT
dc.subjectAdenovirus-vector Vaccinespt_PT
dc.subjectConsensuspt_PT
dc.subjectMosaicpt_PT
dc.subjectPrime-boost Regimenspt_PT
dc.subjectInfecções Sexualmente Transmissíveispt_PT
dc.titleA Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearancept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAdvanced Immunization Technologies
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/280873/EU
oaire.citation.startPage162pt_PT
oaire.citation.titleFrontiers in Immunologypt_PT
oaire.citation.volume7pt_PT
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication0f1935ef-5d43-4ef2-804f-ea502473fea4
relation.isProjectOfPublication.latestForDiscovery0f1935ef-5d43-4ef2-804f-ea502473fea4

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