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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

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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