112 The Development of Enterovirus 71 Vaccine

Enterovirus 71 (EV71) is a major cause of epidemic outbreaks of hand-foot-and-mouth disease (HFMD) worldwide. The virus belongs to the family Picornaviridae, genus Enterovirus. 3 genotypes—A, B, and C and more than 10 sub-genotypes have been identified. After the initial identification of this virus in 1969, some large outbreaks of HFMD have been reported worldwide. EV71-induced HFMD is usually characterized by the formation of maculopapular or vesicular lesions on the skin and oral mucosa, especially on the palms, soles, and mouth. There were a greater number of fatal cases with brainstem encephalitis, pulmonary edema and/or hemorrhage, and cardiopulmonary collapse. Developing effective vaccines is considered a top choice among all control measures. We evaluated the ability of inactivated virus vaccine to elicit neutralizing antibody and to provide protection against lethal infection of EV71 in suckling mice. The purity of EV71 vaccine was up to 96.8% by HPLC identification. The purified EV71 vaccine induced high levels of neutralizing antibodies, these antibodies were shown to be protective against lethal infection when passively transferred to susceptible newborn mice. With a challenge dose of 50LD50 virus/mouse, suckling mice born to dams immunized with inactivated virus showed 100% survival. In preliminary animal trial, no side effects were detected when monkeys were immunized with purified EV71 vaccine either at normal or large doses. The vaccine was approved of the clinical evaluation in 2009. The phase 1/2/3 clinical trail was completed in March 2013. The data suggested that the inactivated EV71 vaccine had a clinically acceptable safety profile and good immunogenicity in healthy children and infants. Our data indicated that inactivated EV71 vaccine is the choice of vaccine preparation capable of fulfilling the demand for effective control.