title: A monoclonal antibody to ameliorate central nervous system infection and improve survival in a murine model of human Enterovirus-A71 encephalomyelitis.
abstract: Enterovirus A71 (EV-A71) encephalomyelitis is an often fatal disease for which there is no specific treatment available. Passive immunization with a specific monoclonal antibody to EV-A71 was used on a murine model of EV-A71 encephalomyelitis to evaluate its therapeutic effectiveness before and after established central nervous system (CNS) infection.
  
  
  
  Mice were intraperitoneally-infected with a mouse-adapted EV-A71 strain and treated with a dose of monoclonal antibody (MAb) daily for 3 days on day 1, 2 and 3 post-infection or for 3 days on 3, 4 and 5 post-infection. Treatment effectiveness was evaluated by signs of infection and survival rate. Histopathology and qPCR analyses were performed on mice sacrificed a day after completing treatment.
  
  
  
  In mock-treated mice, CNS infection was established from day 3 post-infection. All mice treated before established CNS infection, survived and recovered completely without CNS infection. All mice treated after established CNS infection survived with mild paralysis, and viral load and antigens/RNA at day 6 post-infection were significantly reduced.
  
  
  
  Passive immunization with our MAb could prevent CNS infection in mice if given early before the establishment of CNS infection. It could also ameliorate established CNS infection if optimal and repeated doses were given.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Soon Hao
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Kien Chai
authors.initials: KC
authors.lastname: Ong
authors.affiliation: Institute of Health and Community Medicine, Universiti Malaysia Sarawak, 94300, Kota Samarahan, Sarawak, Malaysia.
authors.forename: David
authors.initials: D
authors.lastname: Perera
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. Electronic address: wongkt@ummc.edu.my.
authors.forename: Kum Thong
authors.initials: KT
authors.lastname: Wong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000821:virology*; D029821:Enterovirus A, Human / Q000145:classification / Q000187:drug effects* / Q000276:immunology; D004769:Enterovirus Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000821:virology*; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents
keywords: Enterovirus A71; Monoclonal antibody; Mouse model of human EV-A71 encephalomyelitis; Therapeutic used