Implications of Age-Dependent Immune Responses to Enterovirus 71 Infection for Disease Pathogenesis and Vaccine Design

Epidemics of enterovirus serotype 71 (EV71) infection in Asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. Efforts are underway to develop an effective EV71 vaccine. However, the immunologic correlates of protection against EV71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. Severe disease and death typically occur only in young children, which is likely due in part to a lack of EV71-specific adaptive immunity but possibly also due to age-dependent hyperactive innate immune responses. Infants are the primary targets of EV71 vaccination strategies. Therefore, studies are needed to understand the interplay between age, immunopathology, and severity of EV71 infection to distinguish protective from harmful immune responses and to guide the development of effective EV71 vaccines. This review summarizes our current understanding and outlines the next steps forward.