Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Correlates of relative resistance against low‐dose rectal simian immunodeficiency virus challenges in peripheral blood mononuclear cells of vaccinated rhesus macaques | |
关键词: nonhuman primate; adenovirus; infection; vaccination; immune correlate; gene expression profiles; STEP trial; | |
DOI : 10.1189/jlb.0612287 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Inthisstudy,wecomparedtheimmunogenicityandprotectionfromrepeatedlow‐doseintrarectalSIVmac251challengeintwogroupsofvaccinatedRMs.AnimalswereimmunizedwithliveSIVmac239,whichhadbeenattenuatedbyadeletionofthenefsequence,ortheywerevaccinatedtwicewithanE1‐deletedAdHu5,expressingSIVmac239gag.Thevaccinatedanimalsandacohortofunvaccinatedcontrolanimalswerethenchallenged10timesinweeklyintervalswithlowdosesofSIVmac251givenrectally.OurresultsconfirmpreviousstudiesshowingthatwhereasSIVΔnefprovidessomedegreeofprotectionagainstviralacquisitionafterrepeatedlow‐doserectalSIVmac251challenges,vaccinationwithanAdHu5gagvaccinedesignedtoinduceonlyantiviralTcellresponsesisineffective.Asimmunologicalanalysesofprechallenge,vaccine‐inducedTandBcellresponsesfailedtorevealcorrelatesofprotectionthatdistinguishedthemoresusceptiblefromthemoreresistantvaccinatedanimals,wecarriedoutRNA‐Seqstudiesofpairedpre‐andpostvaccinationsamplestoidentifytranscriptionalpatternsthatcorrelatedwiththedifferencesinresponse.WeshowthatgeneexpressionsignaturesassociatedwiththedelayedSIVinfectionseeninsomeAdHu5gagrecipientswerelargelypresentinprevaccinationsamplesofthoseanimals.Incontrast,therespondingSIVΔnef‐immunizedanimalsshowedapredominanceofvaccine‐inducedchanges,thusenablingustodefineinheritedandvaccine‐inducedgeneexpressionsignaturesandtheirassociatedpathwaysthatmayplayaroleinpreventingSIVacquisition...
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