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Hepatitis C cross-genotype immunity and implications for vaccine development.

cam.issuedOnline2017-09-26
dc.contributor.authorIslam, Nazrul
dc.contributor.authorKrajden, Mel
dc.contributor.authorShoveller, Jean
dc.contributor.authorGustafson, Paul
dc.contributor.authorGilbert, Mark
dc.contributor.authorWong, Jason
dc.contributor.authorTyndall, Mark W
dc.contributor.authorJanjua, Naveed Zafar
dc.contributor.authorThe BC-HTC Team
dc.contributor.orcidIslam, Nazrul [0000-0003-3982-4325]
dc.date.accessioned2018-09-05T12:51:38Z
dc.date.available2018-09-05T12:51:38Z
dc.date.issued2017-09-26
dc.description.abstractWhile about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25-0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27-0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection.
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.27022
dc.identifier.eissn2045-2322
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279654
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41598-017-10190-8
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAdult
dc.subjectAntibodies, Neutralizing
dc.subjectCohort Studies
dc.subjectCross Protection
dc.subjectFemale
dc.subjectGenotype
dc.subjectHepacivirus
dc.subjectHepatitis C
dc.subjectHepatitis C Antibodies
dc.subjectHumans
dc.subjectImmunization, Secondary
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectTreatment Outcome
dc.subjectVaccination
dc.subjectViral Envelope Proteins
dc.subjectViral Hepatitis Vaccines
dc.titleHepatitis C cross-genotype immunity and implications for vaccine development.
dc.typeArticle
dcterms.dateAccepted2017-08-02
prism.issueIdentifier1
prism.publicationDate2017
prism.publicationNameSci Rep
prism.startingPage12326
prism.volume7
rioxxterms.licenseref.startdate2017-09-26
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41598-017-10190-8

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