Correlates of relative resistance against low‐dose rectal simian immunodeficiency virus challenges in peripheral blood mononuclear cells of vaccinated rhesus macaques

[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...

[学科分类] 生理学

[关键词] nonhuman primate;adenovirus;infection;vaccination;immune correlate;gene expression profiles;STEP trial