Malaria VaccineTechnologyRoadmap

Malaria VaccineTechnologyRoadmapAugust 2006

� Malaria Vaccine Technology Roadmap

1 Themalariavaccinefundersgroup,aninformalgroupofsomeofthekeyfundersofmalariavaccinedevelopment,includestheBill&MelindaGatesFoundation,theEuropean&DevelopingCountriesClinicalTrialPartnership,theEuropeanMalariaVaccineInitiative,theEuropeanUnion,thePATHMalariaVaccineInitiative,theUSAgencyforInternationalDevelopment,theUSNationalInstituteofAllergyandInfectiousDisease,theWellcomeTrust,andtheWorldHealthOrganizationInitiativeforVaccineResearch.

2 Thephrase“malariavaccinecommunity”isusedinthisdocumenttorepresentadiversegroupincluding:scientistsfromthepublicandprivatesectorsengagedinmalariavaccineresearchanddevelopment,fundingorganizationssupportingtheseefforts,expertswhodeveloppoliciesrelatedtomalariavaccines,andnationalandglobaldecision-makerswhowillultimatelychoosewhetherandhowtointroduceaneffectivemalariavaccineintopublichealthsystems.ParticipantsintheRoadmapprocessfromthemalariavaccinecommunitycanbefoundonlineat:http://www.malariavaccineroadmap.net.

Scientistshavebeenworkingfordecadestodevelopapreventivemalariavaccine.Whiletheyhavesuccessfullydemonstratedthatsuchavaccineispossible,manychallengescontinuetoimpedeprogressontheroadtoaneffectivemalariavaccine.Asaresult,theMalariaVaccineAdvisoryCommitteetotheWorldHealthOrganization(WHO),coordinatedbytheWHOInitiativeforVaccineResearch(IVR),calledforacollectiveefforttoexploreandaddressthechallenges.ThiseffortresultedintheMalariaVaccineTechnologyRoadmapprocess.

TheMalariaVaccineTechnologyRoadmapprocesswasjointlysponsoredbytheBill&MelindaGatesFoundation,thePATHMalariaVaccineInitiative(MVI),andtheWellcomeTrust.ARoadmapWorkingGroup,consistingofrepresentativesofthesponsorsandIVR,guidedtheprocess.Membersofthemalariavaccinefundersgroup1

servedasactiveparticipantsandadvisors.EnergeticsIncorporatedassistedwiththecoordinationoftheprocess.

Overthecourseofayearandahalf,theRoadmapprocess,describedbelow,involvedmorethan230expertsrepresenting100organizationsfrom35countries(foralistofparticipants,seeAppendixA).Duringthefirsttwomeetings,leadingrepresentativesfromthemalariavaccinecommunity2identifiedthechallengesfacingmalariavaccinedevelopment,establishedavisionandgoal,anddevelopedasharedplantoacceleratemalariavaccinedevelopment.InaseriesofsubsequentStakeholderMeetingsandconsultationthroughtheinternet,theprocesssoughtinputfromthewidermalariavaccinecommunity.

•ParticipantsattheVisionMeeting,heldinOctober2004,inHinxton,UK,identifiedavisionandgoalsanddefinedthechallengeswhichneedtobeaddressedtoaccelerateprogressinmalariavaccinedevelopment.

•TheRoadmapWorkshop,heldinMarch2005,inProvence,France,convenedparticipantstoaddressthechallengesidentifiedduringtheVisionMeeting—creatingactionplansandidentifyingthehighestpriorityinitiativesthatcouldacceleratemalariavaccinedevelopment.

•ThreeStakeholderMeetings,heldinBethesda,Maryland,USA;Durban,SouthAfrica;andOxford,UKduring2005,providedadditionalopportunitiestoshareresultsandtoseekfeedbackfromthebroadermalariavaccinecommunityregardingtheirexpectationsandpotentialrolesinimplementingaholisticmalariavaccinedevelopmentstrategy.

Thesefivemeetingswerethenfollowedbyasynthesisprocess.Keyexpertsreviewedtheresultsofthemeetings,consideringcarefullythecollectiveinputofthemalariavaccinecommunity.Theseexpertsthenprovidedrecommendationsaboutwhichactivitiescouldserveasstrategicareasofinvestmenttoacceleratesignificantlythedevelopmentofamalariavaccine.Basedonfurtherdiscussionswiththemalariavaccinefundersgroup,theserecommendationswerecollatedintothepriorityareasdescribedinthisdocument,theMalaria Vaccine Technology Roadmap.

ExistingfundersofmalariavaccinedevelopmenthaveextendedtheirsupporttotheRoadmapprocessasamechanismforbettercoordinationandimprovedresourcingformalariavaccineresearchanddevelopment.ThemalariavaccinefundersgroupcallsuponnewandexistingpartnerstojointheminsupportingthesepriorityareasbyusingtheRoadmapasapathtocontinuetoaccelerateprogresstowardthegoalofaneffectivemalariavaccine.

Preface

Coverphotoscourtesyof:WendyStoneRichardLordSarahEwart

� Malaria Vaccine Technology Roadmap Malaria Vaccine Technology Roadmap �

Theworldurgentlyneedsamalariavaccinetorelievethehumansufferingassociatedwiththeparasiticdiseasethatkillsmorethanonemillionpeople—mostofthemAfricanchildren—everyyear.Hundredsofmillionsmorepeoplesufferfromtheeffectsofmalaria.Whiledrugs,insecticide-treatedbednets,andotherinterventionsarebeingusedtoreducemalaria’simpact,thediseaseremainsatenaciousadversary.Asafe,effective,andaffordablemalariavaccinewouldcreateapowerfulpublichealthbenefitbyclosingthegapleftbyotherinterventions.

Recognizingthisurgentneed,researchers,funders,andothersinthemalariavaccinecommunityarecommittingtochangingthewaythecommunityworks.Theultimatedriveroftheirindividualeffortsisnotonlytopublishandtofundtheirownresearchbutalsotodevelopaviableproduct—amalariavaccine—thatcansavemillionsoflives.

Therearemanypositivedevelopmentsinthecommunity.Evidenceexiststhatamalariavaccineispossibleandtheglobalvaccineresearchanddevelopmentprocesscontinuestobenefitfromscientificdiscoveries.Themalariavaccinefundinglandscapeisimprovingwithincreasedcooperationamongfundersandrisingphilanthropicandgovernmentcommitments.Mechanismsexistto“push”fundingformalariaresearchanddevelopmentthroughproductdevelopmentpartnershipssuchastheEuropeanMalariaVaccineInitiativeandMVI.Thedevelopmentof“pullmechanisms”suchasadvancemarketcommitments(AMCs)andtheInternationalFinanceFacilityforImmunizationsuggestthatdonorsarebeginningtoplanforthefuturepurchaseofnewvaccinesforneglecteddiseases.Therearealsosignsofincreasinginterestinmalariavaccinedevelopmentbyindustry.

However,themalariavaccinecommunitystandsatacrossroadswithsomechallengesunresolved.Thehurdlestomalariavaccinedevelopmentincludescientificunknowns,inadequatefunding,toolittlecooperationamongscientistsandamongfundingagencies,limitedprivate-sectorinvolvement,mixedlevelsofinterestfromdevelopingcountries,andasyetuncertainmechanismsforprocuringanddistributingasuccessfulvaccine.Whilenoteworthydevelopmentssuchasthoseidentifiedabovehaveimprovedthispicture,betterresourcing,coordination,andcollaborationarestillneeded.

Malaria Vaccines: An Urgent Need1

Vision

ThemalariavaccinecommunitywilldevelopaneffectivevaccinethatpreventsseverediseaseanddeathcausedbyPlasmodium falciparummalariainchildrenunderfiveinsub-SaharanAfricaandotherhighlyendemicregions.Efficientglobalcoordinationandcollaborationwillstimulatethemalariavaccinepipelineandaccelerateprogresstowardsthisachievement.

Strategic Goal

•By2025,developandlicenseamalariavaccinethathasaprotectiveefficacyofmorethan80%againstclinicaldisease3andlastslongerthanfouryears.

Landmark

•By2015,developandlicenseafirst-generationmalariavaccinethathasaprotectiveefficacyofmorethan50%againstseverediseaseanddeathandlastslongerthanoneyear.

3 Whiletherelationshipbetweenvaccineimpactonclinicaldiseaseanddeathiscomplicated,manyscientistsbelievethatavaccinethatprovidesprotectionagainstclinicaldiseasewillprovideanequivalentorhigherprotectionagainstseverediseaseanddeath.

PhotocourtesyofWendyStone

� Malaria Vaccine Technology Roadmap

Malaria Vaccines: An Urgent Need

Toaddressthesechallenges,theglobalmalariavaccinecommunitycametogethertoestablishasharedvisionandgoalsandtoidentifytheactivitiesthatcouldaddresssomeoftheabove-mentionedchallenges.TheresultingMalariaVaccineTechnologyRoadmapoutlinesaplanforhowtheplayerscanworkdifferentlytoacceleratethedevelopmentofaneffectivemalariavaccine,establishingalandmarkof2015forafirst-generationvaccineand2025forasecond-generationvaccine.TocreatetheRoadmap,morethan230experts,representing100organizationsfrom35countries,sharedtheircollectiveknowledgeandinsightsinaseriesofmeetingsheldonthreecontinentsduringanine-monthperiodbetween2004and2005.

Priorities Toachievethevisionandgoals,themalariavaccinecommunityhasidentified11priorityareasthat,ifpursued,couldacceleratethepaceofprogress.Thesepriorities,composedofbothnewinitiativesandongoingeffortsthatrequireadditionalresources,representthetopprioritiesofthecommunity.Theprioritiesfallintofourcategories:research,vaccinedevelopment,keycapacities,andpolicyandcommercialization.Theyaredescribedbrieflybelowandingreaterdetailinthechaptersthatfollow.

Research 1. Developastandardsetofimmunologicalassays

withstandardizedproceduresandreagentstoenablecomparisonsoftheimmuneresponsesofvaccines.

2. Standardizeclinicaltrialdesignandassessmenttoallowcomparisonofdataandtodeterminecorrelatesofprotection.

3. Usestate-of-the-artapproaches,includingfunctionalgenomics,tocharacterizethebiologicalfunctionsofproteinsattheinterfaceofhost-parasiteinteractionsandtoidentifynovelpotentialantigencandidates.

4. Developweb-basedinformation-sharingtoolstostrengthenconnectionsbetweenthelaboratoryandtheclinic.

Vaccine Development 5. Establishasystematicapproachforprioritizing

sub-unitvaccinecandidatesusingacceptedpre-clinicalcriteria.

6. Pursuemulti-antigen,multi-stage,andattenuatedwhole-parasitevaccineapproaches.

Key Capacities 7. Establishreadilyaccessibleformulationandscale-up

processdevelopmentcapacityformalariavaccines. 8. Buildandbroadengoodclinicalpractice(GCP)clinical

trialcapacityinAfricaandothermalaria-endemicregionstoaccommodatethegrowingnumberoftrialsrequiredformalariavaccinedevelopment.

Policy and Commercialization 9. Establishandmaintaincountry-leveldialoguesto

facilitatedecision-makingonmalariavaccinepolicy.

10. Securesustainablefinancingforfutureprocurementofvaccines.

11. Developnovelregulatorystrategiestoexpediteapprovalwhileensuringsafety.

Theseprioritiesoriginatedfromthe55keyactivitiesthatweredrawnfrommorethan225specificscientificandpolicychallengesidentifiedthroughaseriesoffivemeetingsheldonthreecontinentsin2004and2005.Ifappropriatelyresourced,implementingtheseprioritiescouldconsiderablyshortenthetimerequiredtodevelopamalariavaccine.

Moving ForwardInordertoachievethevisionoutlinedintheRoadmap,actionwillberequiredbybothscientistsandfunders.Scientistsandothersinthecommunityshouldcommittofindingabalancebetweenproductivecollaborationandhealthycompetition.Bysharinginformation,scientistscanincreaselearningacrossstudies,acceleratingprogresstowardaneffectivevaccine.Perhapsthestrongestmessagefromthe230expertswhoparticipatedintheprocesswasthatnewresourceswillbeneededtofundresearchofvaccinecandidatesandtoadvancepromisingcandidatesthroughclinicaldevelopment.A2005reportbytheMalariaResearch&DevelopmentAlliancesuggeststhatonlyUS$79millionwasinvestedinmalariavaccinedevelopmentin2004.Morefinancialresourceswillberequiredannuallytoachievethegoalsidentifiedinthisprocess.Inparticular,additionalresourceswillbenecessarytoaddresstheprioritiesidentifiedthroughthisprocess.Finally,increasedcollaborationisneededtoenhancesynergyandreduceredundancyacrossportfolios.

� Malaria Vaccine Technology Roadmap Malaria Vaccine Technology Roadmap �

Atleastuntilahighlyefficaciousmalariavaccineislicensed,themalariavaccinecommunityshouldcontinuetopursuearobustpipelineofcandidatessupportedbyastrongresearchbase.ThereareveryfewmalariavaccinecandidatespoisedtomeettheRoadmap’slandmarkoflicensingafirst-generationvaccineby2015.Scientistsbelievethatarational,evidence-basedapproachisrequiredinordertoachievethegoaloflicensingahighlyefficacioussecond-generationvaccineby2025.Whileevidence-baseddecision-makingremainsessential,criticalgapsinknowledgestillexist.Theseincludethefollowing:

• Incompleteunderstandingofmechanismsofinfectionanddisease.

• Incompleteunderstandingofmechanismsofimmunity.

Progressinunderstandinginfection,disease,andprotectiveimmunityhasbeenslowedbytheinabilitytocomparedatageneratedbyscientistsinthelaboratoryandtheclinic.Theprioritiesdescribedbelowaredesignedtoincreaseknowledgeandmaximizelearninginthecommunitybyimprovingtheabilitytomakecomparisonsacrossdatasetsandbyusingnewtools.

1. Develop a standard set of immunological assays with standardized procedures and reagents to enable comparisons of the immune responses of vaccines.

Themalariavaccinecommunitywouldliketobeabletocompareexperimentalresultsandevaluatevaccine-inducedimmuneresponsesacrossstudiesofsimilarvaccines.Thisrequiresstandardizingcharacterizationprocedures,suchasimmunologicalandfunctionalassaysandthereagentsandprotocolsusedateachstageofmalariavaccineproductevaluation.Paststandardizationeffortshavebeenslowtodevelop,particularlywhentheyhaverequiredtailoredapproaches.Forexample,differentassaysmaybeneededtotestdifferentcandidates,dependingonthecandidate’stargetantigen,protectiveimmunemechanism,andstageofdevelopment.For

Research2Fouractivitiesrepresentthehighestprioritiesneededtoadvancemalariavaccineresearch:

1.Developastandardsetofimmunologicalassayswithstandardizedproceduresandreagentstoenablecomparisonsoftheimmuneresponsesofvaccines.

2.Standardizeclinicaltrialdesignandassessmenttoallowcomparisonofdataandtodeterminecorrelatesofprotection.

3.Usestate-of-the-artapproaches,includingfunctionalgenomics,tocharacterizethebiologicalfunctionsofproteinsattheinterfaceofhost-parasiteinteractionsandtoidentifynovelpotentialantigencandidates.

4.Developweb-basedinformation-sharingtoolstostrengthenconnectionsbetweenthelaboratoryandtheclinic.

PhotocourtesyofPATH

� Malaria Vaccine Technology Roadmap� Malaria Vaccine Technology Roadmap

suchassays,standardizingreagentsandstandardoperatingprocedurescanaidingeneratingresultsthatarerobustandreproducibleandthereforeallowcomparisonamongvaccinecandidates.

Agreeingonstandardimmunologicalassaymethodologiesisnottrivial,butseveraleffortsareunderwaytobegintheprocess.Theseearly-stageeffortsshouldbecommunicatedtoandsupportedbythewidercommunityinordertoensurethattheyresultinstandardassaysthatareamenabletohighthroughputandreflectcurrentscientificunderstanding.Onceestablished,methodstoencourageadherencewiththesestandardsshouldbedeveloped.Forexample,researcherscoulduseanindependentandreadilyaccessiblelaboratorywithbuilt-inassayvalidationandquality-controlstandardstoperformcertainassaysunderblindedconditions.

Ultimately,acompendiumofrecommendedassaysshouldbemadeavailabletotheglobalcommunitywithassociatedstandardizedproceduresandwell-characterizedreagents.Acentralizedlaboratoryor“virtualreferencefacility”consistingofseveralnetworkedlaboratoriescouldupdatetheassaycompendiumasscientificunderstandingadvancesandasmethodsareoptimized.Suchacompendiumwouldrequiresharingofdetailedmethods,reagentsandantigens,immunesera,monoclonalantibodies,andprovisionortrainingofstafftoperformthetests.Onespecificurgentneedisthedevelopmentofnovelimmunoassaystoinvestigatethecellularproductswhichreflectcell-mediatedimmunity.

�. Standardize clinical trial design and assessment to allow comparison of data and to determine correlates of protection.

Malariavaccineclinicaltrialsaredesignedcarefullysoastoensurethatsufficientdataarecollectedaboutthevaccinecandidatebeingevaluatedtoinformsubsequentdecision-makingaboutitsfuturedevelopment.Becausevaccinetrialsrequiresignificantfinancialandhumanresources,scientiststraditionallycontrolcostsbycollecting

onlythedatarequiredtomeasureprimaryandsecondaryendpoints.Thisapproachposestwoproblems.First,definitionsandtypesofendpointsdifferamongclinicaltrials,makingcomparisonsamongcandidatesandacrosstrialseitherdifficultorimpossible.Thisisdueinparttotheneedfordifferentcasedefinitionsindifferentepidemiologicalsettingswithaccompanyingdifferentclinicalandpathologicalmanifestations.Second,oncecandidateshavemovedintoclinicaldevelopment,researchisgenerallyfocusedonmeasuringprotectiveefficacy,withminimalemphasisonexploringbasicresearchquestionsthatremain,suchaselucidatingmechanismsofimmunityandestablishingcorrelatesofprotection.Bothoftheselimitationsmustbeaddressedtomaximizethebenefitoftrials.Inspiteofthecomplexityofmalariapresentation,muchgreaterstandardizationisfeasibleandshouldbepursuedtoincreasetheabilitytocompareresultsacrossstudies.

Whilenotanewidea,standardizationwouldbeachangefromcurrentclinicaltrialpractice.Standardizationoftrialproceduresandendpoints,alongwithappropriateinformedconsent,willenableresearcherstomakewideruseoftrialsamplesanddatasetstoestablishpatternsofcorrelatesofprotection.Byusingastandardsetofmeasurementsthatalltrialresultsobtainedcanemployandsharingtheresultswidely,scientistswillbeabletocomparetrialsindifferentepidemiologicalsettingswithdifferentadjuvantsandantigens.Datafrombothpositiveandnegativecontrolsandstandardsmayofferinsightsandshouldbeincludedindatasets.Clinicaltrialharmonizationwillalsohaveethicalandregulatoryimplications.

Evenwithstandardendpoints,comparisonofvaccineswouldstillbechallenging,givendifferencesinvaccinecandidates,intransmissionsettings,andintheepidemiologiesofthepopulationswherethevaccinesareevaluated.Standardizedendpointsmustbecombinedwithdetailedinformationontrialparticipants,includingage,malariaendemicity,useofindividualmethodsofmalariaprotection,andgeneticbackground.Studiesmustreflecttheepidemiologicaldiversityoftrialsitesandshouldseektodetermineimmuneresponsebyagerangeandparasiteexposure.Caremustalsobetakentoprotecthumansubjects’rightstoconfidentiality.Withclinicaltrialstandardizationandstandardizedassays,scientistscouldsignificantlyenhancethepursuitofreliablecorrelatesofprotection.

� Malaria Vaccine Technology Roadmap� Malaria Vaccine Technology Roadmap Malaria Vaccine Technology Roadmap �

Research

Applyingthesenewtoolstotheparasite’sbloodstage,thephaseintheparasite’slifecyclethatpresentsthegreatestscientificcomplexity,shouldprovetobeparticularlyproductive.Whilesomeeffortstoconsiderblood-stagemalariausinggenomicsareunderway,theseeffortsremainsomewhatfragmented.Amoresystematicapplicationofgenomicstotheerythrocyticstageisneeded,asablood-stagecomponentislikelytobeakeypartofanyhighlyefficaciousvaccine.

Genomicapproachescanalsohelpunderstandtheeffectsofnaturalgenomicdiversity(i.e.,polymorphism)amongparasitesandhumans.Thereasonswhyparasiteandhumanpolymorphismshaveco-evolvedareunknownbutmayhaveimportantimplicationsonunderstandingwhichparasitemoleculesarecriticalfordiseaseandtheepidemiologicalcorrelatesofdiversity.Pairingresearchfacilitiesinendemicandnon-endemiccountriestofacilitateinformationexchangecanaddstructuretolaboratoryandclinicalresearchinteractionsfocusedonassessingpolymorphismanditsimplicationsforvaccinedevelopment.

�. Use state-of-the-art approaches, including functional genomics, to characterize the biological functions of proteins at the interface of host-parasite interactions and to identify novel potential antigen candidates.

Whereasmalariavaccineresearchershavesometimesselectedantigensforevaluationinclinicalsettingsbasedontheircellularinteractions,researcherslackacompleteunderstandingofparasite-hostinteractionstooptimallyguidethesechoices.Genomictoolscanincreasescientists’understandingofthedetailedinteractionbetweentheparasiteanditshost.Forexample,researcherscandeterminewhichgenesareessentialtoparasitesurvivalandwhichareredundant.Thisinsightcanallowresearcherstoidentifyspecificmolecules,orpartsofmolecules,fromtheparasitethatmayrepresentnovelimmunetargets.Achievingaclearunderstandingofproteinfunctiontoinformanddriveantigenselectionrepresentsanewapproachthatcanguidethesystematicapplicationofgenomictools.Scientistscanapplythisunderstandingtoidentifyingnewvaccineconcepts.

Workhasalreadybeguninthisarea.Malariavaccineresearchersarejustbeginningtousenewgenomicandproteomictechnologies.Whilecurrentlycostly,theyoffervaluableinsightsintopotentialnewvaccinetargetsandtypicallyrequireminimalbloodsamples.Effortstousegenomicandproteomictechnologiesshouldaccelerateinpursuitofthe2025goal.Thesetoolscanallowscientiststoidentifyalternativeinvasionpathways,specifymoleculesinvolvedintheseinteractions,anddefinethefunctionofgametocyte,ookinete,andsporozoitesurfaceproteins.Specifictechnologiesthatshouldbedevelopedandappliedtomalariavaccineresearchincludemicroarray-basedtools,targetedmutagenesis,expressionprofiling,andexperimental,high-throughputfunctionalgenomicresearchonhumansandon P. falciparum parasitesfromdiversepopulations.

PhotocourtesyofSarahEwart

� Malaria Vaccine Technology Roadmap

�. Develop web-based information-sharing tools to strengthen connections between the laboratory and the clinic.

Web-basedinformation-sharingtoolsshouldbedevelopedtofacilitatedatasharingamonglaboratoryandclinicalresearchers.Forexample,robustinformationexchangeamonglaboratoryandclinicalresearcherscouldfacilitateseveralessentialstudiesintomechanismsofinnateandacquiredimmunity,includingcross-trialstudies.With

Research

effectiveinformation-sharingsystems,scientistsaroundtheworldcouldexchangeimmunologydataefficiently,sheddinglightontheimmuneresponseandhowitvariesbyepidemiologyandage,andonvaccine-inducedprotectionmechanisms.

Informationsharingmustincludeprocessesandproceduresforprotectingresearchers’abilitytopublishfindingsinpeer-reviewedjournals,competeforgrants,andpursueothertraditionalacademicrewards.Standardsforenteringinformationintoshareddatabases(e.g.,resultsortechniquesthatarereproducible)arealsorequiredtoensurethedataareusefulandappropriateforsubsequentanalysis.TheHumanGenomeProjectofferslessonsforinformation-sharingmethodsandfundingmechanismsthatallowcollaborationanddatasharingwhilesupportingtraditional,healthy,academiccompetition.TheHumanGenomeProjectadoptedaprocessthatpermittedinformationsharingwithinaframeworkofrulesthatprotectedtheresearcher’sabilitytolaterpublishthefindings.Thereisalsoprecedentforsuchcollaborationwithinthemalariacommunity,asevidencedintheP. falciparumgenomeproject.Suchpre-publicationdatasharingcouldaccelerateprogressinvaccinedevelopmentbytwoorthreeyears,thetimetypicallyrequiredtopublishresults.Anynewinformation-sharingprocessshouldbecredible,provideincentivesforparticipation,andbeanavenueforsharingbothnegativeandpositiveresearchresultsthatareimportantforadvancingvaccinedevelopment.

PhotocourtesyofRichardLord

� Malaria Vaccine Technology Roadmap Malaria Vaccine Technology Roadmap �

Vaccinedevelopmentisprimarilyconcernedwithchoosingspecificvaccinecandidates,formulatingthemappropriately,andconductingclinicaltrials.Asisthecasewithmanyotherdiseases,incompleteunderstandingofmalariaimmunologyanddiseasemechanismsmandatesthatscientistsfollowalargelyempiricalmethodforidentifyingvaccinecandidates.

Vaccinedevelopmenteffortsarehinderedbyfivesignificanthurdles:

•Scientistscurrentlylackanadequateunderstandingofmechanismsofdiseaseandimmunity,orcorrelatesofprotection,necessarytorationallyselectcandidatestoproceedtoclinicaltrials.

•Evaluationofavaccineconceptfrominceptiontoproof-of-concepttrialrequiresmanyyearsandmillionsofdollars.

•Therearefarmorepotentialmalariavaccinecandidatesthanthereiscapacityorfundingtoinvestigatethesecandidatesinclinicaltrials.

•Multi-antigenvaccinecandidatesmayofferhigherefficacybutcannotbeevaluatedquicklyintheclinicandmaybecostlytomanufacture.

•Whole-parasiteapproachesmayofferveryhighefficacy,butmaynotbeabletobebroughttothescalenecessarytomeetglobaldemandforamalariavaccine.

Giventhesechallenges,scientistsneedamethodologyforselectingthemostpromisingvaccinecandidatesforfurtherevaluationwhileminimizingunfruitfulinvestmentsinlesspromisingorredundantapproaches.Accordingly,establishingasystematic,rigorousrationaleforselectingwhichsub-unitvaccinecandidatestoadvancetoclinicaltrialsisaprimaryconcerninvaccinedevelopment.Atthesametime,becausescientistsdonotknowwhethersub-unitapproacheswillbeabletoofferhighlyefficaciousvaccines,alternativeapproachessuchaswhole-parasiteandcombinationvaccinesshouldalsobepursued.

Vaccine Development3Twoimportantnewactivitiescanleadtoadvancesinmalariavaccinedevelopment:

5.Establishasystematicapproachforprioritizingsub-unitvaccinecandidatesusingacceptedpre-clinicalcriteria.

6.Pursuemulti-antigen,multi-stage,andattenuatedwhole-parasitevaccineapproaches.

PhotocourtesyofMollyMort

10 Malaria Vaccine Technology Roadmap10 Malaria Vaccine Technology Roadmap

�. Establish a systematic approach for prioritizing sub-unit vaccine candidates using accepted pre-clinical criteria.

Malariaresearchershavelongdebatedwaysofrankingvaccinecandidates—aprocessthatrequirescriteriatoorganizethemyriadopportunitiesavailableinthepost-genomicera.AccordingtotheWorldHealthOrganization,therearemorethan30potentialmalariavaccinecandidatesindevelopment.Themajorityofthesearebasedonrecombinantproteinsandoverone-halfconsistofasingleantigen.4Withlimitedresourcesavailabletoevaluatethesecandidates,prioritizationisrequired.Asystematic,evidence-basedapproachforprioritizingvaccinecandidateswouldexpeditetheprogressionofpromisingvaccineconceptsalongthedevelopmentpathwayandpromotegreaterconfidenceamongscientistsandfundersthatinvestmentsarefocusedonthebestcandidates.

Pre-clinicalrankingcriteriamightincludefactorssuchas:•Typeofimmuneresponseinducedbythecandidate.•Abilitytogenerateafunctionalandstableformofthe

antigen.•Abilitytomeasureantimalariaimmuneeffectorfunction

in vitro.•Potentialformulationsofthecandidate.•Abilitytomanufactureandscaleupproductionofthe

candidate.

Researchersshouldthenapplytheseandothercriteriatorankvaccinecandidates,particularlythosebasedonthesameantigens,inanobjectivemanner.Whilethisapproachmaybemosthelpfulforprioritizingantigens,adjuvants,andformulationsforsub-unitvaccines,itcouldbeextendedtoincludeothervaccinationstrategiessuchasvector-basedorwhole-parasiteapproaches.

Systematicselectioncriteriawillnotguaranteethesuccessoftop-rankedcandidates.Infact,prioritizingcandidatesrunstheriskofde-prioritizingacandidatethatmightultimatelyofferthebestprotection.However,inascientificcommunitywithlimitedresourcesandcorrelatesofprotectionyetunknown,developingandcontinuingtorefineasystematicandevidence-basedapproachtocandidateselectioncanhelptofocusinvestmentsoncandidatesthatappeartobethemostpromising,giventoday’sbestscientificknowledge.

Whilesystematiccriteriacanbeusedtoinformgo/no-godecisionsforclinicaldevelopment,thecriteriashouldnotdisqualifyacandidatealtogether.Instead,thecriteriacouldhelptofocusresearchonpoorlyscoringantigensbyidentifyingknowledgegaps,includingthebiologicalimplicationsofpolymorphicvariationinthefield.Asnewinsightsaregained,antigenscanbere-evaluatedfortheirpotential.Inaddition,theprioritizationcriteriamustberegularlyreviewedandrevisedtoreflectthemostadvancedscientificunderstanding.

4 WorldHealthOrganization(WHO)InitiativeforVaccineResearch,Portfolio of candidate malaria vaccines currently in development, March 2005,Geneva:WHO;2005.Availableathttp://www.who.int/vaccine_research/documents/en/malaria_table.pdf

PhotocourtesyofPATH

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�. Pursue multi-antigen, multi-stage, and attenuated whole-parasite vaccine approaches.

GiventhecomplexityofP. falciparumandtheearlystageofmanymalariavaccinedevelopmentefforts,adiversityofvaccineapproachesshouldbepursued.Recently,individualsub-unitvaccinecandidateshavebeentheprimaryresearchfocusandconstitutethemajorityofmalariavaccineconcepts.Resultsfromresearchintosub-unitvaccinestodatehaveledsomescientiststobelievethatthesevaccinesbythemselvesmaynotachievethehighestpossibleefficacy.Thesecandidatesmayhavetobecombinedwithothercandidatestocreatemulti-antigenvaccines.Somescientistsbelievethatsuchapproaches,alongwithattenuatedwhole-parasiteapproaches,mayofferthegreatestpotentialtoproducehighlyefficaciousvaccinesthatprovidelong-termprotectionindiverseepidemiologicalsettings.

Multi-antigenvaccines,likelytargetingdifferentstagesintheparasite’slifecycle,mayconferbetterprotectionthanavaccinebasedonasingleantigen.Oneapproachmaybetopursueamulti-stagevaccinebycombiningtwopartiallyeffectivevaccinecandidatesthattargetdifferentstagesoftheparasite’slifecycletoachievegreateroverallefficacythroughadditiveorsynergisticeffects.Ultimately,suchvaccinesmayincludemultipleantigensfromthesameparasitelife-cyclestageinconjunctionwithantigenstargetingotherstages.Suchanapproachmayalsoavoidvaccinefailurecausedbypolymorphicvariationsindiverseparasitepopulations.Thismethodintroduceshigherformulationandproductioncostsandentailsmorecomplexinteractionsbetweenthevaccineandtheimmunesystem.

Vaccine Development

Whole-parasiteapproachesarenotnewinvaccinedevelopment.Experimentalvaccinationwithattenuatedparasiteshasbeenshowntoofferprotectionagainstchallengewithmalariaparasites.However,vaccinesbasedonattenuatedmalariaparasitesfacesignificantobstaclesbecausetheyaredifficulttocharacterizeandmanufactureinlargequantities. In vitro culturesofsporozoitesandasporozoitechallengemodelareneededtosupportfurtherexplorationoftheseconcepts.Whiletheobstaclesassociatedwiththeseapproachesaresignificant,newtechnologiessuchasgeneticattenuationofsporozoites,newmethodstogeneratelargenumbersofsporozoites,andthecompletionofalow-doseblood-stagetrialinnaïvevolunteersoffernewpromiseforpossiblebreakthroughs.Improvedanalyticaltoolsnowallowformorecompletecharacterizationofwhole-parasitevaccineconcepts,andhumantrialsusinggeneticallyattenuatedparasitesareneeded.Whileregulatoryandsafetyissuesremain,somescientistsbelievethatvaccinecandidatesusingwhole-parasiteapproachesarefeasibleandmeritcontinuedattentionbecauseoftheirpotentialtodemonstratehighefficacy.

PhotocourtesyofRobertC.Thompson

1� Malaria Vaccine Technology Roadmap

1� Malaria Vaccine Technology Roadmap Malaria Vaccine Technology Roadmap 1�

Whileanumberofpromisingmalariavaccinecandidatesareundergoingvariousstagesofdevelopment,thecapacitytoevaluatethemremainslimited.Formulationandprocessdevelopmentexpertiseandcapacityareprimarilyconcentratedinpharmaceuticalcompanieswhere,withfewexceptions,thereislimitedinvestmentinmalariavaccinedevelopment.Clinicaltrialhumanresourceandinfrastructurecapacityinmalaria-endemiccountriesislimited.InordertoachievethegoalsoftheRoadmapprocess,thesekeycapacitiesmustbedeveloped.

Tostrengthenthecapacitytoundertakeformulationandprocessdevelopmentandtoconductclinicaltrials,themalariavaccinecommunitymustovercomethefollowingchallenges:•Thedifficultymanyresearchershaveinaccessingadequate

processdevelopmentandformulationcapabilitiesandthemostpromisingadjuvants.

•TheimbalancebetweenthegrowingnumberofpotentialmalariavaccinecandidatesandthesmallnumberofGCPclinicaltrialsitesinmalaria-endemicregions,whichlimitsthecapacitytoevaluatethesecandidates.

Addressingthesechallengescouldenhancethemalariavaccinecommunity’sabilitytodevelopefficaciousformulationsandevaluatetheminclinicaltrialsinmalaria-endemicregions.

�. Establish readily accessible formulation and scale-up process development capacity for malaria vaccines.

Themalariavaccinecommunityrequiresadditionalformulationandprocessdevelopmentresourcesandexpertise.Althoughthemalariavaccinecommunityhasstrongbasicscienceandpre-clinicalexpertise,ithasmuchlessexperiencewithchemistry,manufacturing,andcontrolissues.Manyresearchersinthecommunity(whodonotworkforpharmaceuticalcompanies)lackaccesstotheproteincharacterization,formulation,andprocessdevelopmentcapabilitiesnecessarytoassesswhetherthoseformulationscanbeeconomicallymanufacturedinagood

Key Capacities4Twoimportantandnewactivitiescouldestablishcriticalcapacitiesneededtoacceleratemalariavaccinedevelopment:

7.Establishreadilyaccessibleformulationandscale-upprocessdevelopmentcapacityformalariavaccines.

8.BuildandbroadenGCPclinicaltrialcapacityinAfricaandothermalaria-endemicregionstoaccommodatethegrowingnumberoftrialsrequiredformalariavaccinedevelopment.

PhotocourtesyofSiriWood

1� Malaria Vaccine Technology Roadmap

manufacturingpracticeenvironment.Further,nosinglepartnercurrentlyinvolvedinmalariavaccinedevelopmenthastherequiredcapacitytomanufactureandformulatethewiderangeofvaccineconceptsbeingdeveloped.

Establishinganaccessibleprocessdevelopmentcenterorsetofcollaboratingresearchorganizationsthatoperateasa“virtualcenter”wouldaddressthischallenge.Eitherapproachwouldmostlikelyrepresentapartnershipamongacademic,commercialorcontract,andgovernmentinstitutions.Thecentershouldsupportrapidsharingofinformation,helpdefinescopeandobjectivesforanyformulationorprocessdevelopmentprojectpursued,andadviseonintegratingprocessdevelopmentandformulationwiththelargervaccinedevelopmentprocess.Appropriategovernanceandtransparencywillberequiredforthisapproachtogainwidespreadacceptanceamongscientistsandfundingagencies.

�. Build and broaden GCP clinical trial capacity in Africa and other malaria endemic regions to accommodate the growing number of trials required for malaria vaccine development.

IntheabsenceofathoroughunderstandingofimmuneresponsestoP. falciparum andmechanismsofdisease,clinicalevaluationofvaccinecandidatesistheonlywaytomeasureefficacyanddurationofprotection.Evaluationofthesecandidatesinmalaria-endemicareasprovidesthemostreliableinformationregardinghowthevaccineislikelytoperformunderconditionsofnaturalexposure.Further,candidatesmustbeevaluatedinareaswithdiversetransmissionsettingsandepidemiologies.Currently,therearefewclinicaltrialsitesinAfricathatcanconductmalariavaccinetrials.Inordertoaccommodatethegrowingnumberofcandidatesproceedingthroughthepipeline,themalariavaccinecommunitymuststrengthenandensurethesustainabilityofexistingsiteswhilemakingsurethatthesitesmaintaintheirrelevanceforscientificresearch.

Whileanumberofclinicaltrialsitesalreadyexistinmalaria-endemicareasofAfrica,fewhavesustainablebusinessmodelswithstaffwhocanconducttrialsunderGCPconditions.Multiplesitesarerequiredtoensuresufficientcapacityinthefuture.Toprepareclinicalsitesforevaluationofmalariavaccinecandidates,theymusthavereliablefundingandwell-trainedstaff.Sitesalsorequirelocalleadershipwithoutstandingprojectmanagementskillstomanagestaffandresourcesandtosecureconsistent,sustainedresearchproductivityandcorrespondingfunding.Eachsitealsorequiresfinancialaccountingstructuresandspecializedpersonnel(e.g.,certifiedclinicalresearchcoordinators,datamanagementqualityassurance,andclinicalresearchmonitors).Strongerbiomedicalethicscapacityisalsoneededtoensureethicalstandardsareapplied.Viablecareerdevelopmentpathwaysandjobsecurityarerequiredtoattractandretaininvestigatorsandstafftoensurethatacriticalmassofcompetent,skilledpersonnelisavailabletosupportthesesitesinthelongterm.

Inadditiontothestrengthofthesiteitself,anumberofscientificfactorsaffectasite’sappropriatenessformalariavaccinetrials.Clinicaltrialswithapromisingvaccinecandidatewilleventuallyneedtobeconductedinavarietyoftransmissionandepidemiologicalsettingssoastodemonstratetheefficacyofthecandidateinthosesettings.Malariadiseaseburdensneartrialsitesgenerallydeclineovertimeasinterventions,suchasinsecticide-treatednets,insecticidespraying,anddrugs,becomemorewidelyusedeitherduringthecourseofclinicaltrialsorthroughhigherthanaveragecommunityeducationefforts.Whilethisphenomenonisunquestionablypositiveforlocalpopulations,trialsiteswithoutsignificantmalariadiseaseburdenarelessattractiveformalariavaccineproof-of-concepttrialsbecausethesamplesizesrequiredtodemonstratetheeffectofthevaccinebecomelargerandlessattainable.Finally,sitesmustbeabletoconductlong-termfollowupoftrialsubjects,especiallyforthepurposesofidentifyingpotentialsecondaryeffects.Guidelinesshouldbedevelopedtoencouragelong-termmonitoringandassessmentofsafetyanddurationofprotection.Improvingdemographicsystemsthatcancharacterizethestudiedpopulationandfollowsubjectsforfiveorsixyearswillenablelonger-termmonitoring.

Key Capacities

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Policy & Commercialization5Threeactivitiesrepresentthehighestprioritiesforaddressingmalariavaccinepolicyandcommercialization:

9. Establishandmaintaincountry-leveldialoguestofacilitatedecision-makingonmalariavaccinepolicy.

10. Securesustainablefinancingforfutureprocurementofvaccines.

11. Developnovelregulatorystrategiestoexpediteapprovalwhileensuringsafety.

Inadditiontoovercomingtechnicalandscientificchallenges,thesuccessfuldeliveryofamalariavaccinerequiresthatpolicyandcommercializationissuesbeaddressedtoensurethatpeopleinendemiccommunitieshavereliableaccesstothevaccineinatimelymanneronceefficacyhasbeendemonstrated.Effectivepolicyandcommercializationeffortsmustaddressfourcriticalchallenges:

•Uncertainregulatorypathwaysforlicensingavaccineforuseprimarilyindevelopingnations.

• Incompleteunderstandingofhowandwhethercountriesshouldintroducemalariavaccinesamongmalaria-controlmechanismsandinterventionstargetingotherdiseases.

•Reluctanceofdonorsandpolicy-makingbodiestoplanforthepurchaseanddeploymentofmalariainterventionsthatarestillindevelopment.

•Limitedmarketpullforprivate-sectorinvestmentsinthedevelopmentofvaccinestargetingsomeofthepoorestpopulationsintheworld.

Thesechallengesarenotnew,butongoingeffortstoaddressthemhavebeenunder-fundedandsometimesfragmented.Morefocusedeffortscanhelptosendtherightsignalsthatwillstimulatethevaccinedevelopmentpipelinetodayandeaseeventualintroductionofavaccine.

�. Establish and maintain country-level dialogues to facilitate decision-making on malaria vaccine policy.

Leadersofmalaria-endemiccountrieswillultimatelymakedecisionsaboutwhethertointroducealicensedmalariavaccine,yettherehasbeenlimitedformalcontactregardingmalariavaccineswithcountryleaderstodate.Byestablishingcontactwithnationalstakeholders,themalariavaccinecommunitycanexploretheirdecision-makingprocessesinordertoensurethatthecommunitywillbeabletoprovidethedatatosupporttheprocess.Inlearningwhichdataarerequiredbydecision-makers,themalariavaccinecommunitywillbeable

PhotocourtesyofSarahEwart

1� Malaria Vaccine Technology Roadmap1� Malaria Vaccine Technology Roadmap

tocollectthedataduringclinicaldevelopment.Makingthenecessarydataavailablefordecision-makingwouldminimizeunnecessarydelaysintheuptakeofalicensedmalariavaccine.

Decision-makersrequireabetterunderstandingoftheimpactofamalariavaccine.Criticaldatapointsincludeanunderstandingofthemalariadiseaseburdenandtheeffectivenessofexistinginterventions,thevaccine’spotentialimpactonhealth,thevaccine’scost-effectivenessandaffordability,howthevaccinewouldbeintegratedintoexistinghealthservices,andcommunityperceptionsofthevaccine.Someofthesedataalreadyexistandsomewillhavetobecollected.Intheabsenceofrigorousdata,someofthisinsightcanbeobtainedthroughmodels.However,existingmodelsmustberefinedornewmodelsmustbedevelopedwherethesedatacanbesupportedandvalidatedwithclinicaltrialinformation.AsmalariatypicallyoccursalongsideotherepidemicssuchasHIV/AIDSandtuberculosis,analysesshouldbeextendedtoassessmalariainterventionsalongsidethosetargetingotherdiseases.Atthesametime,public-healthbudgetsinmostmalaria-endemicnationsareconstrained,diseaseinterventionscompeteforfunds,andtheknowledgeneededforinformeddecision-makingisincomplete.Country-leveldialoguesshouldattempttoaddressthecomplexinterplayamongdiseasesindiverseepidemiologicalsettingstosupportinformeddecisionmaking.

Researchersinthemalariavaccinecommunityshouldcontinuetoengagewithkeystakeholderstoensurethatpreparationsaremadetoconsiderafuturemalariavaccine.Theseandothercountry-leveldialogueswouldcomplementongoingeffortsatthegloballeveltounderstandandcommunicatetheimplicationsofintroducingamalariavaccineintopublic-healthsystemsacrossAfricaandotherhighlyendemicregions.

10. Secure sustainable financing for future procurement of malaria vaccines.

Althoughamalariavaccinewillnotbelicensedforfivetotenyearsormore,countriesanddonorsshouldbegintoplanforitspurchasenow.Endemiccountriesrequiresustainable,long-termfinancingmechanismstoensurethattheycanacquiremalariavaccineswithoutstraininglimitedpublichealthbudgets.Whencountriesbecomeconfidentthatfinancingwillbeavailable,theyaremorelikelytosignalstrongdemandforamalariavaccine.Sustainablefinancingandstrongcountrydemandwillstimulateadditionalinvestmentinmalariavaccinedevelopmentbypharmaceuticalcompaniesandothers.

AMCs,inwhichprocurementagenciesenterintobindingcontractstopurchasevaccineswhentheybecomeavailable,representonefinancingapproachthathasreceivedattentioninrecentyears.FinanceministersfromtheGroupofSevenindustrializednationsareevaluatingAMCsandthepotentialimplementationofapilotAMCin2006.Ifmalariaischosenforthispilotprogram,specificdesignworkonhowtostructurethecommitmentwillberequiredtosupportpursuitofthe2025goalandthe2015landmark.

Arelatedfinancingtoolisthedevelopmentofaviablepricingmodelthatincorporatestheuniquecostsandbenefitsofcommercializingvaccinesthatexclusivelytargetdiseasesofthepoor.Pharmaceuticalfirmscurrentlyengagedinvaccinedevelopmentcanhelptoidentifysuitablefactorsforinclusioninsuchamodel(e.g.,tieredpricingfordifferentfinancingscenariosorphases,factoringthevalueofpublicrelationsintopricing,andcostsharingwithphilanthropicorganizations).Asuccessfulmodelcouldencourageindustryparticipationwithoutcompromisingcorporatefiscalhealth.

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11. Develop novel regulatory strategies to expedite approval while ensuring safety.

Regulatorypathwaysforvaccinesexclusivelytargetingpopulationsindevelopingnationsarenotyetestablished.Thepredominantglobalregulatoryagencies(i.e.,theUSFoodandDrugAdministration[FDA]andtheEuropeanMedicinesEvaluationAgency)customarilydonotlicenseproductsthatarenotintendedforuseintheirpopulations.ManyAfricancountriesdonothavetheirownestablishedregulatoryagenciesand,insomecases,nationalregulatorymechanismsareunclear.Accordingly,regulatoryreviewofafuturemalariavaccinemayseriouslydelaytheintroductionofamalariavaccine.Forthesereasons,novelregulatoryapproachesareneededtoexpeditevaccineapprovalanddistributionwhileensuringthatthehighestsafetystandardshavebeenmet.

Toreducetheunpredictabilityofthefutureregulatorypathwayofmalariavaccines,regulatoryagenciesshouldoffertransparentanddetailedguidelinesdescribingtheirprocessesforconsideration,especiallyforcommunities—likethemalariavaccinecommunity—whoarepursuingthedevelopmentofproductsprimarilyintendedfordevelopingcountries.Atthesametime,malaria-endemiccountriesshouldestablishnationalpoliciesandregulatoryprocesses.Allnationalregulatoryagenciesrequirearangeofskillstosupporteffectivevaccinelicensureanddeployment.

Policy & Commercialization

PhotocourtesyoftheDavidandLucilePackardFoundation

Strategiestodevelopandnavigateregulatorypathwayscanriseabovetheplaneofmalariavaccinedevelopment.TheFDA’sCriticalPathInitiativeisoneexampleofaregulatoryagencyseekingtoworkmorecloselywiththepharmaceuticalindustrytoacceleratevaccineanddrugdevelopment.Partnershipswithothervaccinedevelopersmayhelptospreadthecostofdevelopingsharedregulatoryprocessesfordevelopingnationsamongmultiplecommunities,avoidduplicatingefforts,andensureconsistencyacrosshealthinterventions.

1� Malaria Vaccine Technology Roadmap

1� Malaria Vaccine Technology Roadmap Malaria Vaccine Technology Roadmap 1�

Developinganeffectivemalariavaccineisanenormouschallenge.ThisRoadmap,developedwiththeinsightsof230expertsfrom35nations,reflectstheglobalnatureofthechallengeandtheworld-wideresponserequired.TheRoadmapattemptstoorganizethemalariavaccinecommunityaroundasharedvisionandgoalsandidentifies11prioritiesthatholdgreatpotentialforefficientlyadvancingmalariaresearch.However,thepublicationoftheRoadmapdocumentwillaccomplishverylittlewithoutfurtheraction.TheRoadmapcanguidethemalariavaccinecommunitytoimprovetheeffectivenessandrelevanceofindividualendeavorswhilecontributingtoalargerefforttodevelopalife-savingproduct.

TheeventualsuccessoftheRoadmapdependsontheongoingcommitmentofalltorealizethevisionoftheprocess—todevelopapreventivemalariavaccinethatcansavelives.Themalariavaccinecommunitywillhavetoriseabovetheirindividualandorganizationaleffortsinordertoachievethelandmarkofdevelopingafirst-generationvaccineby2015andthegoalofdevelopingahighlyefficacioussecond-generationvaccineby2025.Whiletherearenoguaranteesofsuccess,achievingtheprioritiesidentifiedinthisRoadmapwillhelpthecommunitytoaccelerateprogresstowardthedevelopmentofamalariavaccineandtomaximizetheeffectivenessoftheresourcesinvested.

Membersofthemalariavaccinefundersgroup,eachassociatedwithagenciesfundingmalariavaccinedevelopmentandthemselvescontributorstotheRoadmapprocess,havecommittedtogreatercoordination,collaboration,andpartnershipinsupportingsomeoftheprioritiesidentifiedbytheRoadmap.SomeoftheseorganizationshavealreadybeguntoworktogethertoaddresstheRoadmap’spriorities.AfurtheroutcomeoftheRoadmapprocesswastherecognitionoftheneedforincreasedcommitmentsfromexistingdonors,combinedwithfundsfromnewdonors,toinvestintheprioritiesidentifiedthroughthisprocessandrealizethegoaloftheRoadmapby2025.

Withsomanylivesatstake,themalariavaccinecommunityshouldworktogethertopursuetheseactivitiesaggressively.Thereisnotimetowaste.MillionsofchildreninAfricaandothermalaria-endemicregionsarewaitingforaneffectivemalariavaccine.Scientistsknowthatwithsufficientresourcesandincreasedcollaboration,theycanandwilldevelopone.WitharenewedcommitmentandenergyfromthemalariavaccinecommunitytofocusontheprioritiesoutlinedintheRoadmap,scientistswillbeabletoacceleratethedevelopmentoftheirsharedgoal:aneffectivemalariavaccinethatcansavemillionsoflives.

Implementation6TheeventualsuccessoftheRoadmapdependsontheongoingcommitmentofalltorealizethevisionofthe

process—todevelopapreventivemalariavaccinethatcansavemillionsoflives.

PhotocourtesyofPATH

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AppendixA The following people participated in the Malaria Vaccine Technology Roadmap Process:

Dr.OlusojiAdeyi,WorldBank;Mr.MartinAdjuik,NavrongoHealthResearchCentre;Dr.SusanAdu-Amankwah,NoguchiMemorialInstituteforMedicalResearch;Mr.GeorgeAkanlu,NavrongoHealthResearchCentre;Ms.PatriciaAkweongo,NavrongoHealthResearchCentre;Dr.AliAlloueche,ChironVaccines,Italy;Dr.PedroAlonso,HospitalClinicBarcelona;Dr.EvelinaAngov,WalterReedArmyInstituteofResearch;Dr.ThomasAnvorigiya,NavrongoHealthResearchCentre;Dr.RipleyBallou,GlaxoSmithKlineBiologicals;Dr.WilliamBancroft,ScienceApplicationsInternationalCorporation;Dr.DrorBaruch,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.JohnBarnwell,CentersforDiseaseControl;Dr.JuliaBarrett,BiologicsConsultingGroup;Mr.GirindreBeeharry,Bill&MelindaGatesFoundation;Prof.PeterBeverley,EdwardJennerInstituteforVaccineResearch;Dr.TedBianco,TheWellcomeTrust;Prof.FredBinka,INDEPTH-Network;Dr.JoelBreman,FogartyInternationalCenter;Mr.AlanBrooks,ThePATHMalariaVaccineInitiative;Prof.GrahamBrown,UniversityofMelbourne;Dr.JosephBruder,GenVec,Inc.;Dr.DanielCarucci,FoundationfortheNationalInstitutesofHealth–GrandChallenges;Dr.JoeCohen,GlaxoSmithKlineBiologicals;Dr.MartinComberbach,GeneMedixplc;Dr.DavidConway,LondonSchoolofHygieneandTropicalMedicine,MedicalResearchCouncil,TheGambia;Dr.RossCoppel,MonashUniversity;Dr.BrendanCrabbe,TheWalterandElizaHallInstituteofMedicalResearch;Dr.JonDaugherty,U.S.DepartmentofHealthandHumanServices/U.S.FoodandDrugAdministration;Dr.EugeneDavidson,GeorgetownUniversity;Dr.DondeSavigny,SwissTropicalInstitute;Dr.CharlesdeTaisne,Sanofi-Pasteur;Dr.StevenDerrick,U.S.FoodandDrugAdministration,CenterforBiologicsEvaluationandResearch(CBER);Dr.CarterDiggs,U.S.AgencyforInternationalDevelopment;Dr.DanielDodoo,NoguchiMemorialInstitute;Dr.DeniseDoolan,NavalMedicalResearchCenter;Dr.OgobaraDoumbo,UniversityofMali-BKO;Dr.PierreDruilhe,InstitutPasteur;Dr.FilipDubovsky,ThePATHMalariaVaccineInitiative;Dr.KennethEckels,WalterReedArmyInstituteofResearch;Dr.RobertEdelman,UniversityofMaryland;Mr.BillEnright,GenVec,Inc.;CommanderJudithEpstein,NavalMedicalResearchCenter;Dr.AlexEzeh,AfricanPopulationandHealthResearchCenter;Dr.BernardFanget,FlamelTechnologies;Ms.MichelleFolsom,ProgramforAppropriateTechnologyinHealth;Prof.JuliaFox-Rushby,BrunelUniversity;Dr.MartinFriede,WorldHealthOrganization;Mr.EdwardGaliwango,IgangaDSS-Uganda;Dr.BlaiseGenton,SwissTropicalInstitute;Prof.MichaelGood,QueenslandInstituteofMedicalResearch;Dr.MichaelGottlieb,FoundationfortheNationalInstitutesofHealth;Dr.AricGregson,CenterforVaccineDevelopment;Prof.BrianGreenwood,LondonSchoolofHygieneandTropicalMedicine;Dr.MargaretGyapong,DodowaHealthResearchCentre,GhanaHealthService;Dr.AbdullahelHadi,WatchProject;Dr.LeeHall,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.AndreasHeddini,MultilateralInitiativeonMalaria;Dr.CaroleHeilman,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Lt.Col.DonaldGrayHeppner,WalterReedArmyInstituteofResearch;Dr.KobusHerbst,AfricanCentre;Dr.SocratesHerrera,InternationalMalariaVaccineandDrugTestingCenter;Prof.AdrianHill,UniversityofOxford;Dr.AbrahamHodgson,NavrongoHealthResearchCentre;Dr.StephenHoffman,Sanaria;Dr.AnthonyHolder,NationalInstituteforMedicalResearch;Dr.AndreasHoltel,EuropeanCommission;Dr.DouglasHoltzman,Bill&MelindaGatesFoundation;Dr.

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LarsHviid,Rigshospitalet;Dr.RonaldIacocca,EliLillyandCompany;Dr.SureshJadhav,SerumInstituteofIndia,Ltd.;Dr.StephanieJames,GrandChallengesinGlobalHealth,FoundationfortheNationalInstitutesofHealth;Dr.DavidKaslow,Vical;Dr.Marie-PauleKieny,WorldHealthOrganization;Prof.WenKilama,AfricanMalariaNetworkTrust;Dr.ShirimaKizito,IfakaraHealthResearchandDevelopmentCentre;Dr.RichardKlausner,Bill&MelindaGatesFoundation;Dr.JackKloeber,JohnsonandJohnson;Dr.KwadwoKoram,NoguchiMemorialInstitute;Dr.JingyeeKou,U.S.FoodandDrugAdministration,CenterforBiologicsEvaluationandResearch;Dr.BocarKouyate,CentredeRechercheenSante;Dr.NirbhayKumar,JohnsHopkinsUniversity;Prof.DominicKwiatkowski,OxfordUniversity;Dr.DavidLanar,WalterReedArmyInstituteofResearch;Dr.AntonioLanzavecchia,InstituteforResearchinBiomedicine;Dr.FrankLee,CompoundTherapeutics,Inc.;Dr.RoseLeke,UniversityofYaounde,Cameroon;Ms.AnniqueLennon,ThePATHMalariaVaccineInitiative;Dr.OdileLeroy,TheEuropeanMalariaVaccineInitiative;Dr.GailLevine,NavalMedicalResearchCenter,MalariaProgram;Dr.RuthLevine,CenterforGlobalDevelopment;Dr.ShengLi,ThePATHMalariaVaccineInitiative;Dr.LawrenceLightner,U.S.ArmyMedicalResearch&MaterialCommand;Dr.KeithLimbach,NavalMedicalResearchCenter;Dr.CaroleLong,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.JeffLyon,WalterReedArmyInstituteofResearch;Dr.BruceMacLeod,UniversityofSouthernMaine;Dr.AlanMagill,WalterReedArmyInstituteofResearch;Dr.SiddharthaMahanty,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.MichaelMakanga,European&DevelopingCountriesClinicalTrialsPartnership;Dr.FrankMalinoski,OxxonTherapeutics,Inc.;Dr.ElissaMalkin,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Mr.ChrisMaltby,ThePATHMalariaVaccineInitiative;Dr.KevinMarsh,TheKenyaMedicalResearchInstitute;Dr.LauraMartin,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.EllisMcKenzie,NationalInstitutesofHealth;Dr.LouisMiller,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Prof.AnneMills,LondonSchoolofHygiene&TropicalMedicine;Dr.PascoalMocumbi,European&DevelopingCountriesClinicalTrialsPartnership;Prof.KazuhikoMoji,InstituteofTropicalMedicine;Prof.MalcolmMolyneux,TheMalawi-Liverpool-WellcomeTrustResearchProgramme;Dr.VaseeMoorthy,ThePATHMalariaVaccineInitiative;Dr.MelindaMoree,ThePATHMalariaVaccineInitiative;Dr.SheldonMorris,U.S.FoodandDrugAdministration,CenterforBiologicsEvaluationandResearch;Dr.HassanMshinda,IfakaraHealthResearchandDevelopmentCentre;Dr.SallyMtege,IfakaraHealthResearchandDevelopmentCentre;Dr.IvoMueller,PNGInstituteofMedicalResearch;Dr.EleutherMwageni,RufijiDSS;Dr.Abdollah(Abdi)Naficy,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.ElizabethNardin,NewYorkUniversityMedicalCenterandSchoolofMedicine;Dr.DavidNarum,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.RoseNathan,IfakaraHealthResearchandDevelopmentCentre;Prof.ChrisNewbold,OxfordUniversity;Dr.FrancineNtoumi,MedicalResearchUnitASH;Dr.RuthNussenzweig,NewYorkUniversityMedicalCenterandSchoolofMedicine;Dr.ChristianOckenhouse,WalterReedArmyInstituteofResearch;Dr.JosephineOcran,NoguchiMemorialInstituteforMedicalResearch;Dr.KwadwoOdeiAntwi-Agyei,GhanaHealthServices;Dr.AggreyOloo,WorldHealthOrganization,

RegionalOfficeforAfrica;Dr.SethOwusu-Agyei,GhanaHealthService;Dr.MarcelaParra,U.S.FoodandDrugAdministration;Dr.StevenPhillips,ExxonMobilCorporation;Dr.ChristopherPlowe,UniversityofMaryland;Dr.ReginaRabinovich,Bill&MelindaGatesFoundation;Dr.TheodoreRandolph,UniversityofColorado;Dr.StevenReed,InfectiousDiseaseResearchInstitute;Dr.ZarifahReed,WorldHealthOrganization,InitiativeforVaccineResearch;Dr.KevinReilly,IndependentConsultant;Dr.ThomasRichie,NavalMedicalResearchCenter;Dr.MagdaRobaloCorreiaeSilva,WorldHealthOrganization;Dr.WilliamRodgers,NavalMedicalResearchUnit3;Dr.AnaRodriguez,NewYorkUniversitySchoolofMedicine,DepartmentofParasitology;Dr.StevenRosenthal,U.S.FoodandDrugAdministration,CenterforBiologicsEvaluationandResearch;Prof.SarahRowland-Jones,MedicalResearchCouncil;Dr.MikeRoy,ScienceApplicationsInternationalCorporation;Dr.PhilipRussell,AlbertB.SabinVaccineInstitute;Dr.OsmanSankoh,INDEPTHNetwork;Dr.JeraldSadoff,AerasGlobalTBVaccineFoundation;Dr.RainerSauerborn,UniversityofHeidelberg;Dr.RobertSauerwein,RadboudUniversityNijmegenMedical;Dr.AllanSaul,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.FranciscoSaute,NationalMalariaControlProgrammeofMozambique;Ms.MaryKateScott,ScottDevelopmentGroup;Dr.MosheShmuklarsky,ScienceApplicationsInternationalCorporation;Dr.AlanShaw,Merck&Co.,Inc.;Dr.PhotiniSinnis,NewYorkUniversitySchoolofMedicine;Dr.BlossomSmith,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Prof.PeterSmith,LondonSchoolofHygieneandTropicalMedicine;Dr.ThomasSmith,SwissTropicalInstitute;Dr.ValSnewin,TheWellcomeTrust;Mr.BoStenson,TheGlobalAllianceforVaccinesandImmunization;Dr.AnnStewart,WalterReedArmyInstituteofResearch;Dr.JacobSweiry,TheWellcomeTrust;Ms.WendyTaylor,BIOVenturesforGlobalHealth;Dr.StephenTollman,UniversityoftheWitwatersrand;Dr.MaritaTroye-Blomberg,StockholmUniversity;Dr.LornaVanderZanden,TheUSArmyMedicalMaterielDevelopmentActivity;Dr.YukikoWagatsuma,UniversityofTsukuba;Dr.TonuWali,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.MarkWalport,TheWellcomeTrust;Dr.MatsWahlgren,KarolinskaInstitute,MIM;Dr.PhilipWhalen,WhalenManagementGroup;Mr.PiersWhitehead,VaxGen,Inc.;Ms.WendyWoods,BostonConsultingGroup;Dr.YiminWu,NationalInstitutesofHealth,NationalInstituteofAllergyandInfectiousDiseases;Dr.FidelZavala,JohnsHopkinsUniversity

Working Group: Dr.PaulineBeattie,TheWellcomeTrust;Dr.RuthBranston,TheWellcomeTrust;Dr.PatGoodwin,TheWellcomeTrust;Dr.DougHoltzman,BillandMelindaGatesFoundation;Dr.Marie-PauleKieny,WorldHealthOrganization;Dr.MelindaMoree,ThePATHMalariaVaccineInitiative;Dr.ReginaRabinovich,BillandMelindaGatesFoundation;Dr.ZarifahHussainReed,WorldHealthOrganization;Dr.ValSnewin,TheWellcomeTrust

Roadmap Team: Mr.RossBrindle,EnergeticsIncorporated;Ms.PagetDonnelly,EnergeticsIncorporated;Mr.JackEisenhauer,EnergeticsIncorporated;Ms.SarahEwart,ThePATHMalariaVaccineInitiative;Dr.IrenePetrick,PennsylvaniaStateUniversity;Dr.MargaretPinder,IndependentConsultant;Dr.MichaelRoy,ScienceApplicationsInternationalCorporation

�� Malaria Vaccine Technology Roadmap

Formoreinformation,pleasevisitwww.MalariaVaccineRoadmap.net