Characterization of an Anti-lymphocyte Function-associated Antigen-1 Antibody in a Simian Immunodeficiency Virus–Pig-tailed Macaque (Macaca nemestrina) Model

摘要

Thesimianimmunodeficiencyvirus(SIV)/pig-tailedmacaque(Macacanemestrina)modelofacquiredimmunedeficiencysyndrome(AIDS)isapowerfulsysteminwhichtostudycelladhesionmoleculesandretroviralpathogenesisinvivo.Preliminaryexperimentswereconductedtoexaminetheroleoflymphocytefunction-associatedantigen1(LFA-1)inearlySIVinfectioninvivobyusinganLFA-1monoclonalantibody(MHM.23)specifictohumanLFA-1.Invitrostudiesrevealedthatatconcentrationsof#8805;20#59157;g/ml,MHM.23blockedLFA-1-mediatedadhesionandT-cellactivation(90%)ofpig-tailedmacaqueperipheralbloodmononuclearcells(PBMCs).Inaddition,SIVmac239infectionofmacaquecellswasinhibitedinadose-dependantmannerbyMHM.23.AdministrationofMHM.23topig-tailedmacaquesinhibitedLFA-1#8211;ICAM-1-mediatedactivityinvivoandmaintainedbindingonmacaquecellsfor#8804;4d.OurinvitrostudiesindicatedthatatanMHM.23concentrationof20#59157;g/ml,macaquePBMCswerecompletelysaturated.Ourinvivostudiesdeterminedthat5mg/kgMHM.23intravenouslyevery24hwasrequiredtomaintainsaturatinglevelsandinhibitLFA-1#8211;ICAM-1functioninpig-tailedmacaques.