An auto-antibody identified from phenotypic directed screening platform shows host immunity against EV-A71 infection

Background: Enterovirus A71 (EV-A71) is a neurotropic virus which may cause severe neural complications, especially in infants and children. The clinical manifestations include hand-foot-and-mouth disease, herpangina, brainstem encephalitis, pulmonary edema, and other severe neurological diseases. Although there are some vaccines approved, the post-marketing surveillance is still unavailable. In addition, there is no antiviral drugs against EV-A71 available. Methods: In this study, we identified a novel antibody that could inhibit viral growth through a human single chain variable fragment (scFv) library expressed in mammalian cells and panned by infection with lethal dose of EV-A71. Results: We identified that the host protein α-enolase (ENO1) is the target of this scFv, and anti-ENO1 antibody was found to be more in mild cases than severe EV-A71 cases. Furthermore, we examined the antiviral activity in a mouse model. We found that the treatment of the identified 07-human IgG₁ antibody increased the survival rate after virus challenge, and significantly decreased the viral RNA and the level of neural pathology in brain tissue. Conclusions: Collectively, through a promising intracellular scFv library expression and screening system, we found a potential scFv/antibody which targets host protein ENO1 and can interfere with the infection of EV-A71. The results indicate that the usage and application of this antibody may offer a potential treatment against EV-A71 infection.