Duration of vaccine efficacy against malaria: 5th year of follow-up in children vaccinated with RTS,S/AS02 in Mozambique

Abstract

AprimaryconcernfortheRTS,Smalariavaccinecandidateisdurationofprotection.TheongoingPhaseIIItrialreportedevidenceofwaningefficacywithinthefirstyearfollowingvaccination.MultiplePhaseIIbtrialsdemonstratedearlywaningofefficacy.ThelongestdurationofprotectionforRTS,Srecordedtodatewasinatrialofacohortof1605Mozambicanchildrenage1–4yratthetimeofimmunization(C1),whichshowedanoverallefficacyagainstclinicalmalariaof30.5%over43subsequentmonthsofsurveillance.AsignificantreductioninparasiteprevalenceinRTS,Svaccineesindicatedthatthevaccinecontinuedtoprotectattheendofthisperiod.Althoughfollow-upforrecordingincidentcasesofclinicalmalariawasstoppedat45months,wewereinterestedinevidenceoffurtherdurabilityofprotection,andrevisitedthecohortat63months,recordingthesecondarytrialendpoint,prevalenceofasexualPlasmodiumfalciparumparasitemia,intheRTS,Sandcomparatorvaccinegroupsasaproxyforefficacy.Asacomparator,wealsovisitedthecontemporaneouscohortof417children(C2),whichshowedwaningefficacyafter6monthsoffollow-up.Wealsoassessedanti-circumsporozoiteantibodytiters.TheseresultswerecomparedwiththoseofotherPhaseIIbtrials.PrevalenceofparasitemiawasnotsignificantlylowerintheRTS,S/AS02groupcomparedtocomparatorgroupsinC1(57[119%]Vs62[128%];p=0.696)orC2(30[226%]Vs35[276%];p=0.391),despiteelevatedantibodytiters,suggestingthatprotectiondidnotextendto5yearsaftervaccination.ThisisincontrasttotheearlierassessmentofparasitemiainC1,wherea34%lowerprevalenceofparasitemiawasobservedintheRTS,S/AS02groupatmonth45.ComparisonwithotherPhaseIItrialshighlightsacomplexrelationshipbetweenefficacy,ageandtransmissionintensity.RTS,S/AS02providedpartialprotectionfromclinicalmalariaforatleast3.5yearsinC1.Durationofprotectionmaydependonenvironmentalcircumstances,suchaschangingmalariatransmission,andspecialattentionshouldbegiveninthePhaseIIItrialtoidentifyingfactorsthatmodifylongevityofprotection