Formaldehyde-Inactivated Whole-Virus Vaccine Protects a Murine Model of Enterovirus 71 Encephalomyelitis against Disease

Abstract

Enterovirus 71 (EV71) causes childhood hand, foot, and mouth disease and neurological complications, and no vaccines or therapeutic drugs are currently available. Formaldehyde-inactivated whole-virus vaccines derived from EV71 clinical isolates and a mouse-adapted virus (MAV) were tested in a mouse model of EV71 encephalomyelitis. After only two immunizations, given to mice at 1 and 7 days of age, the MAV vaccine protected mice at 14 days of age from disease. Tissues from immunized mice were negative for virus by viral culture, reverse transcriptase PCR, immunohistochemistry analysis, and in situ hybridization. Cross-neutralizing EV71 antibodies to strains with genotypes B3, B4, and C1 to C5 generated in immunized adult mice were able to passively protect 14-day-old mice from disease.

A Neonatal Mouse Model of Coxsackievirus A16 for Vaccine Evaluation

“…To develop an EV71 vaccine, animal models for the neonatal mouse, the cynomolgus monkey, and the rhesus monkey have been established and improved. These animal models confirmed the protective role of vaccine in inducing neutralizing antibody and also promoted the development of the EV71 vaccine (1,10,33,35). Until our study, no animal model had been developed to evaluate the protective efficacy of the CA16 vaccine.…”

“…Recently, diseases induced by CA16 and the development of CA16 vaccine have received increasing attention, and several companies in mainland China have begun to launch CA16 vaccine development projects. The successful development of an EV71 vaccine benefits not only from other well-developed inactivated enterovirus vaccines but also from the establishment and application of a neonatal mouse model and a macaque model for evaluating the clinical or preclinical protection effects (1,10,33,35). For CA16, a study using a CA16 animal experiment was first reported in 1951 (43).…”

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

“…Multiple EV-71 subgenogroups can cocirculate during an outbreak (1,46,82), and rapid switching among subgenogroups has become increasingly common, perhaps caused by virus importation, evolution of novel lineages, or other factors (14,39,48,57,82). Although broadly neutralizing antibodies against selected EV-71 subgenogroups have been reported in animal models (6,27,49,54,83), the degree of cross-protection and the potential for EV-71 escape evolution in humans remain uninvestigated and unknown. Therefore, addressing the dynamic relationships between the rapidly evolving EV-71 and its human hosts is critical in gaining a better understanding of the disease.…”

Tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in Chinese healthy adults and children

“…Recently, several EV71 candidate vaccines have been successfully developed and evaluated in animal models 10 and further study in human are expected. In January 2011, a formaldehydeinactivated, alum-adjuvanted EV71 vaccine (genotype C4) developed by Beijing Vigoo Biological Co., Ltd. (Beijing, China) was approved to undergo a phase 1 clinical trial, with the aim of evaluating the tolerability of the new vaccine in healthy adults and children.…”