title: In vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors.
abstract: BACKGROUND
  Enterovirus type 71 (EV71) causes large outbreaks with significant mortality among young children, and no specific antiviral treatment is currently available. Antibody-based therapy represents a promising alternative strategy for lethal EV71 infection. Our previous data has shown that anti-EV71 neutralization antibodies were present in a significant proportion of blood donors in China.
  
  
  OBJECTIVE
  To produce a new human intravenous immunoglobulin (IVIG) product containing high titer anti-EV71 neutralizing antibodies and investigate its therapeutic efficacy against lethal EV71 infection in a murine model.
  
  
  METHODS
  Plasma units that contained high titer neutralizing antibodies from selected Chinese donors were pooled and processed into pharmaceutical grade IVIG preparations according to the standard procedure. The efficacy of these EV71-specific IVIG product was characterized in vitro by neutralization assay and in vivo by suckling mouse protection testing. The therapeutic effects against lethal EV71 challenge were further assayed in a suckling mouse model.
  
  
  RESULTS
  About 12% of the normal plasma units were selected and pooled to manufacture the EV71-IVIG preparations, and in vitro and in vivo efficacy data showed that these EV71-specific IVIG preparations were enriched with neutralizing antibodies against EV71. Furthermore, treatment with EV71-specific IVIG was evidenced to confer protection against lethal EV71 challenge in a dose- and time-dependent manner in the suckling mouse model.
  
  
  CONCLUSIONS
  This preclinical study indicates that these "tailor-made" EV71-IVIG preparations manufactured from selected plasma donors in EV71-endemic areas may represent a promising therapeutic option for the lethal EV71 infections, and further clinical trials should be warranted in the future.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20th Dongda Street, Beijing 100071, China.
authors.forename: Rui-Yuan
authors.initials: RY
authors.lastname: Cao
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Han
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Xue
authors.initials: X
authors.lastname: Tian
authors.forename: Man
authors.initials: M
authors.lastname: Yu
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000302:isolation & purification / Q000494:pharmacology*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000302:isolation & purification / Q000494:pharmacology*; D002681:China; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000188:drug therapy* / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D012376:Rodent Diseases / Q000188:drug therapy / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D016756:Immunoglobulins, Intravenous