Antibody and T Cell Responses in Reciprocal Prime-Boost Studies with Full-Length and Truncated Merozoite Surface Protein 1–42 Vaccines.docVIP

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Antibody and T Cell Responses in Reciprocal Prime-Boost Studies with Full-Length and Truncated Merozoite Surface Protein 1–42 Vaccines.doc

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Antibody and T Cell Responses in Reciprocal Prime-Boost Studies with Full-Length and Truncated Merozoite Surface Protein 1–42 Vaccines

AntibodyandTCellResponsesinReciprocalPrime-Boost StudieswithFull-LengthandTruncatedMerozoite SurfaceProtein1–42Vaccines KaePusic*,DanielleClements,SophieKobuch,GeorgeHui UniversityofHawaii,SchoolofMedicine,DepartmentofTropicalMedicine,Honolulu,Hawaii,UnitedStatesofAmerica Abstract TheP.falciparumMerozoiteSurfaceProtein1–42(MSP1-42)isoneofthemoststudiedmalariasubunitvaccinecandidates. TheN-terminalfragmentofMSP1-42,MSP1-33,isprimarilycomposedofallelicsequences,andhasbeenshowntopossessT helperepitopesthatinfluenceprotectiveantibodyresponsestowardtheC-terminalregion,MSP1-19.AtruncatedMSP1-42 vaccine,Construct33-I,consistingofexclusivelyconservedTepitoperegionsofMSP1-33expressedintandemwithMSP1- 19, was previously shown to be a more effective immunogen than the full-length MSP1-42 vaccine. Here, by way of reciprocal priming/boosting immunization regimens, we studied the immunogenicity of Construct 33-I in the context of recognitionbyimmuneresponsesinducedbythefull-lengthnativeMSP1-42protein,inordertogaugetheeffectsofpre- and post-exposures to MSP1-42 on vaccine induced responses. Judging by immune responsiveness, antibody and T cell responses, Construct 33-I was effective as the priming antigen followed by full-length MSP1-42 boosting, as well as the boosting antigen following full-length MSP1-42 priming. In particular, Construct 33-I priming elicited the broadest responsiveness in immunized animals subsequently exposed to MSP1-42. Moreover, Construct 33-I, with its conserved MSP1-33specificTcellepitopes,wasequallywellrecognizedbyhomologousandheterologousallelicformsofMSP1-42. SerumantibodiesraisedagainstConstruct33-IefficientlyinhibitedthegrowthofparasitescarryingtheheterologousMSP1- 42 allele. These results suggest that Construct 33-I maintains and/or enhances its immunogenicity in an allelic or strain transcendingfashionwhendeployedinpopulationshavingpriororsubsequentexposurestonativeMSP1-42s. Citation: Pusic K, Clements D, Kobuch S, Hui G (2013) Antibody and T Cel