A monoclonal antibody to ameliorate central nervous system infection and improve survival in a murine model of human Enterovirus-A71 encephalomyelitis

Abstract

Keywords:Enterovirus A71 Monoclonal antibody Therapeutic used Mouse model of human EV-A71 encephalomyelitis a b s t r a c t Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis

“…Briefly, the serum samples were serially diluted up to 1:512 and mixed equally with 100 CCID 50 of EV-A71. 28 The samples were then incubated at 4 °C overnight before inoculation onto Vero cell monolayers in 96-well plates; the samples were cultured for seven days at 36 °C. Monoclonal mouse anti-EV-A71 antibody was used as a positive control, as previously described.…”

Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

“…BB1A5 recognized a linear epitope spanning amino acids 136–155 in the VP2, and passive transfer of BB1A5 was able to provide 100% protection for the new-born mice challenged with a mouse-adapted EV-A71 strain. Besides that, another group identified a mAb designated as 3D1 belonging to the IgM isotype generated by immunizing mice with a mouse-adapted EV-A71 strain [68]. They demonstrated that passive immunization using 3D1 prevented central nervous system (CNS) infection.…”