A bispecific broadly neutralizing antibody against enterovirus 71 and coxsackievirus A16 with therapeutic potential

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of hand, foot and mouth disease (HFMD), which affects children worldwide and is often associated with neurological complications. At present, there is no vaccine or cure available for simultaneous EV71 and CA16 infection, posing a great need to develop novel strategies for the treatment of this disease. Here, we engineered four bispecific antibodies using variable fragments of monoclonal antibodies (mAbs) from EV71- and CA16-specific neutralizing antibodies. The engineered bispecific antibody Bs(scFv)4-IgG-1 exhibits remarkable cross-reactivity against EV71 and CA16 and has a more potent cross-neutralization than its parental antibodies. Furthermore, we showed that Bs(scFv)4-IgG-1 conferred 100% therapeutic efficacy against single or mixed EV71 and CA16 infections in mice. Our study provides important insights into bispecific antibody engineering against enterovirus and will inform new curative treatment options for HFMD.