Bicistronic DNA Vaccines Simultaneously Encoding HIV, HSV and HPV Antigens Promote CD8+ T Cell Responses and Protective Immunity.docVIP

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Bicistronic DNA Vaccines Simultaneously Encoding HIV, HSV and HPV Antigens Promote CD8+ T Cell Responses and Protective Immunity.doc

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BicistronicDNAVaccinesSimultaneouslyEncodingHIV,HSVandHPVAntigensPromoteCD8TCellResponsesandProtectiveImmunity

BicistronicDNAVaccinesSimultaneouslyEncodingHIV, HSVandHPVAntigensPromoteCD8 TCellResponses andProtectiveImmunity + ViniciusC.Santana1,MarianaO.Diniz1,FranciscoA.M.O.Cariri1,ArmandoM.Ventura1,Ede′cioCunha- Neto2,RafaelR.Almeida2,MarcoA.Campos3,GracielaK.Lima3,Lu?′sC.S.Ferreira1* 1DepartmentofMicrobiology,BiomedicalSciencesInstitute,UniversityofSa?oPaulo,Sa?oPaulo,Brazil,2LaboratoryofClinicalImmunologyandAllergy-LIM60,Divisionof ClinicalImmunologyandAllergy,DepartmentofMedicine,UniversityofSa?o PauloSchoolofMedicine,Sa?o Paulo,Brazil,3Rene′ RachouResearchCenter,Fiocruz,Belo Horizonte,Brazil Abstract Millionsofpeopleworldwidearecurrentlyinfectedwithhumanpapillomavirus(HPV),herpessimplexvirus(HSV)orhuman immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunologicalapproachesrepresentsahopefortheeradicationoflatentinfectionand/orvirus-associatedcancer.Todate, attempts todevelop vaccines against these viruses have beenmainly based on amonovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purposeinmind,wetestedtwobicistronicDNAvaccines(pIRESIandpIRESII)thatencodetheHPV-16oncoproteinE7and theHIVproteinp24bothgeneticallyfusedtotheHSV-1gDenvelopeprotein.Micei.m.immunizedwiththeDNAvaccines + mountedantigen-specificCD8 Tcellresponses,includinginvivocytotoxicresponses,againstthethreeantigens.Under experimentalconditions,thevaccinesconferredprotectiveimmunityagainstchallengeswithavacciniavirusexpressingthe HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8 T cell- + dependent responses is feasible and may aid in the developm