Antibody Responses to a Novel Plasmodium falciparum Merozoite Surface Protein Vaccine Correlate with Protection against Experimental Malaria Infection in Aotus Monkeys.docVIP

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Antibody Responses to a Novel Plasmodium falciparum Merozoite Surface Protein Vaccine Correlate with Protection against Experimental Malaria Infection in Aotus Monkeys.doc

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Antibody Responses to a Novel Plasmodium falciparum Merozoite Surface Protein Vaccine Correlate with Protection against Experimental Malaria Infection in Aotus Monkeys

AntibodyResponsestoaNovelPlasmodiumfalciparum MerozoiteSurfaceProteinVaccineCorrelatewith ProtectionagainstExperimentalMalariaInfectionin AotusMonkeys DavidR.Cavanagh1*,ClemensH.M.Kocken2,JohnH.White1,GraemeJ.M.Cowan1,KaySamuel3, MartinA.Dubbeld2,AnnemarieVoorberg-vanderWel2,AlanW.Thomas2,JanaS.McBride1, DavidE.Arnot1 1Institute of Immunology and Infection Research, Center for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom,2BiomedicalPrimateResearchCenter,DepartmentofParasitology,Rijswijk,TheNetherlands,3ScottishNationalBloodTransfusionService,CellTherapyGroup, UniversityofEdinburgh,Edinburgh,UnitedKingdom Abstract TheBlock2regionofthemerozoitesurfaceprotein-1(MSP-1)ofPlasmodiumfalciparumhasbeenidentifiedasatargetof protectiveimmunitybyacombinationofseroepidemiologyandparasitepopulationgenetics.Immunogenicitystudiesin smallanimalsandAotusmonkeyswereusedtodeterminetheefficacyofrecombinantantigensderivedfromthisregionof MSP-1 as a potential vaccine antigen. Aotus lemurinus griseimembra monkeys were immunized three times with a recombinantantigenderivedfromtheBlock2regionofMSP-1ofthemonkey-adaptedchallengestrain,FVOofPlasmodium falciparum, using an adjuvant suitable for use in humans. Immunofluorescent antibody assays (IFA) against erythrocytes infected with P. falciparum using sera from the immunized monkeys showed that the MSP-1 Block 2 antigen induced significantantibodyresponsestowholemalariaparasites.MSP-1Block2antigen-specificenzyme-linkedimmunosorbent assays(ELISA)showednosignificantdifferencesinantibodytitersbetweenimmunizedanimals.Immunizedanimalswere challengedwiththevirulentP.falciparumFVOisolateandmonitoredfor21days.Twooutoffourimmunizedanimalswere able to control their parasitaemia during the follow-up period, whereas two out of two controls developed fulminating parasitemia. Parasite-specific serum antibody titers measured by IFA were four-fold higher in protected animals than in unprotected