Immunotherapeutic effect of anti-PrP monoclonal antibodies in transmissible spongiform encephalopathy mouse models: pharmacokinetic and pharmacodynamic analysis

被引：6

作者：

Feraudet-Tarisse, Cecile ^{[1
,2
]}

Andreoletti, Olivier ^{[1
]}

Morel, Nathalie ^{[2
]}

Simon, Stephanie ^{[2
]}

Lacroux, Caroline ^{[1
]}

Mathey, Jacinthe ^{[1
]}

Lamourette, Patricia ^{[2
]}

Relano, Aroa ^{[3
]}

Maria Torres, Juan ^{[3
]}

Creminon, Christophe ^{[2
]}

Grassi, Jacques ^{[2
]}

机构：

[1] Ecole Natl Vet Toulouse, UMR INRA ENVT 1225, Interact Hote Agent Pathogene, F-31076 Toulouse, France

[2] CEA Saclay, IBiTec S, Serv Pharmacol & Immunoanal, F-91191 Gif Sur Yvette, France

[3] Ctr Invest Sanidad Anim CISA INIA, Madrid 28130, Spain

来源：

JOURNAL OF GENERAL VIROLOGY | 2010年 / 91卷

关键词：

CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN; IMMUNOMETRIC ASSAYS; BLOOD-TRANSFUSION; CELL-CULTURES; REPLICATION; MICE; RESISTANT; EXPOSURE; VCJD;

D O I：

10.1099/vir.0.018077-0

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Prion diseases are transmissible neurodegenerative disorders for which no therapeutic or prophylactic regimens exist. Passive immunization with appropriate antibodies directed against the cellular form of the prion protein (PrPC) can delay the onset of prion disease after peripheral infection, but mechanisms and parameters determining their in vivo efficacy remain unknown In the present study, we characterized the main pharmacokinetic properties of anti-PrP antibodies in different mouse models expressing various levels of PrPC (Prnp(0/0), C57BL/6 and tga20 mice) in correlation with therapeutic effect. Plasma levels of free antibodies, total endogenous PrPC and PrPC antibody complexes were monitored after a single intraperitoneal monoclonal antibody (mAb) injection Efficacy in delaying PrPSc peripheral accumulation seemed to be associated with mAb capacity to form long-lasting complexes with endogenous PrPC in the plasma. In agreement with previous observations on cellular models of transmissible spongiform encephalopathy infection, we observed that injection of anti-PrP antibodies induced a large (up to 100-fold) increase in circulating PrPC. Finally, the most efficient antibody extended the lifespan of infected animals greatly These results allowed us to define critical characteristics of anti-PrP mAbs associated with therapeutic efficacy and could constitute a useful reference for designing optimized passive immunotherapies for prion diseases

引用

页码：1635 / 1645

页数：11

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