Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.
Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan town, Miaoli County, Taiwan.
Hsuen-Wen
HW
Chang
Yi-Wen
YW
Lin
Hui-Min
HM
Ho
Min-Han
MH
Lin
Chia-Chyi
CC
Liu
Hsiao-Yun
HY
Shao
Pele
P
Chong
Charles
C
Sia
Yen-Hung
YH
Chow
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control / Q000821:virology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D051116:Receptors, Scavenger / Q000235:genetics; D019562:Viral Load
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human