Broad Antibody Mediated Cross-Neutralization and Preclinical Immunogenicity of New Codon-Optimized HIV-1 Clade CRF02_AG and G Primary Isolates 英文参考文献.docVIP

Broad Antibody Mediated Cross-Neutralization and Preclinical Immunogenicity of New Codon-Optimized HIV-1 Clade CRF02_AG and G Primary Isolates 英文参考文献.doc

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Broad Antibody Mediated Cross-Neutralization and Preclinical Immunogenicity of New Codon-Optimized HIV-1 Clade CRF02_AG and G Primary Isolates 英文参考文献

BroadAntibodyMediatedCross-Neutralizationand PreclinicalImmunogenicityofNewCodon-Optimized HIV-1CladeCRF02_AGandGPrimaryIsolates SimonM.Agwale1,2*,JosephC.Forbi1,2,FrankNotka3,TerriWrin4,JensWild5,RalfWagner3,5 ,Hans Wolf5 1ClinicalVirologyLaboratory,InnovativeBiotech,Keffi/Abuja,Nigeria,2FrederickInnovativeTechnologyCenter,InnovativeBiotech,Frederick,Maryland,UnitedStatesof America,3GeneArtAG,Regensburg, Germany,4Monogram Biosciences Inc., SouthSan Francisco, California, United States ofAmerica, 5Molecular Microbiology and GeneTherapyUnit,InstituteforMedicalMicrobiologyandHygiene,UniversityofRegensburg,Regensburg,Germany Abstract Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizingantibodiesareassumedtobepivotaltothesuccessofaprophylacticvaccinebutpreviousattemptstomake animmunogencapableofgeneratingneutralizingantibodiestoprimary‘‘streetstrain’’isolateshaveresultedinresponses ofverylimitedbreadthandpotency.Theobjectiveofthestudywastodeterminethebreadthandstrengthofneutralizing antibodiesagainstautologousandheterologousprimaryisolatesinacohortofHIV-1infectedNigeriansandtocharacterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regionspredominatedbyHIV-1CRF02_AGandGsubtypes.EnvelopevectorsfromapanelofprimaryNigerianisolateswere constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (MonogramBiosciencesInc,USA)toassessthebreadthandpotencyofneutralizingantibodies.Theimmediategoalofthis studywasrealizedbytherecognitionofthreebroadlycross-neutralizingsera:(NG2-cladeCRF02_AG,NG3-cladeCRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with agag sequence(CladeG)andconsensustat(CRF02_AGandG)antigenshavebeencodon-optimized,synthesized,clonedand evaluatedinBALB/cmice.TheintramuscularadministrationoftheseplasmidD

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