Protection against High-Dose Highly Pathogenic Mucosal SIV Challenge at Very Low Serum Neutralizing Titers of the Antibody-Like Molecule CD4-IgG2 英文参考文献.docVIP

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Protection against High-Dose Highly Pathogenic Mucosal SIV Challenge at Very Low Serum Neutralizing Titers of the Antibody-Like Molecule CD4-IgG2 英文参考文献.doc

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Protection against High-Dose Highly Pathogenic Mucosal SIV Challenge at Very Low Serum Neutralizing Titers of the Antibody-Like Molecule CD4-IgG2 英文参考文献

ProtectionagainstHigh-DoseHighlyPathogenicMucosal SIVChallengeatVeryLowSerumNeutralizingTitersof theAntibody-LikeMoleculeCD4-IgG2 PascalPoignard1,2,3*,BrianMoldt1,KarlaMaloveste3¤a,Noe¨lieCampos3¤b,WilliamC.Olson4, EvaRakasz5,DavidI.Watkins5,6,DennisR.Burton1,7 * 1DepartmentofImmunologyandMicrobialScienceandIAVINeutralizingAntibodyCenter,TheScrippsResearchInstitute,LaJolla,California,UnitedStatesofAmerica, 2InternationalAIDSVaccineInitiative,NewYork,NewYork,UnitedStatesofAmerica,3TheCentred’ImmunologiedeMarseille-Luminy,andInstitutNationaldelaSante′ etdelaRechercheMedicale,andCentreNationaldelaRechercheScientifique,Marseille,France,4ProgenicsPharmaceuticals,Inc.Tarrytown,NewYork,UnitedStatesof America, 5Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 6Department of Pathology,UniversityofMiami,Miami,Florida,UnitedStatesofAmerica,7RagonInstituteofMassachusettsGeneralHospital,MassachusettsInstituteofTechnology,and Harvard,Boston,Massachusetts,UnitedStatesofAmerica Abstract Passive transfer studies using monoclonal or polyclonal antibodies in the macaque model have been valuable for determining conditions for antibody protection against immunodeficiency virus challenge. Most studies have employed hybrid simian/human immunodeficiency virus (SHIV) challenge in conjunction with neutralizing human monoclonal antibodies.PassiveprotectionagainstSIV,particularlythepathogenicprototypevirusSIVmac239,hasbeenlittlestudied because ofthe paucity of neutralizing antibodies to this virus. Here, weshow that theantibody-like molecule CD4-IgG2 potently neutralizes SIVmac239 in vitro. When administered by an osmotic pump to maintain concentrations given the shorthalf-lifeofCD4-IgG2inmacaques,themoleculeprovidedsterilizingimmunity/protectionagainsthigh-dosemucosal viral challenge to a high proportion of animals (5/7 at a 200mg dose CD4-IgG2 and 3/6 at a 20mg dose) at serum concentrationsbelow1.5mg/ml.Theneutr