Abstract
BackgroundCirculating enterovirus 71 (EV-A71)-associated hand, foot, and mouth disease is on the rise in the Asian-Pacific region. Although animal models have been developed using mouse-adapted EV-A71 strains, mouse models using primary EV-A71 isolates are scarce. Lethal animal models with circulating EV-A71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation.ResultsIn this study, we established a lethal mouse model using primary EV-A71 isolates from patients infected with serotypes that are currently circulating in humans. We also characterized the dose-dependent virulence and pathologic changes of circulating EV-A71 in this mouse model. Most importantly, we have established this mouse model as a suitable system for EV-A71 vaccine evaluation. An inactivated EV-A71 vaccine candidate offered complete protection from death induced by various circulating EV-A71 viruses to neonatal mice that were born to immunized female mice. The sera of the immunized dams and their pups showed higher neutralization titers against multiple circulating EV-A71 viruses.ConclusionsThus, our newly established animal model using primary EV-A71 isolates is helpful for future studies on viral pathogenesis and vaccine and drug development.
Highlights
Circulating enterovirus 71 (EV-A71)-associated hand, foot, and mouth disease is on the rise in the Asian-Pacific region
EV-A71 and Coxsackievirus A16 (CV-A16) are the two major etiological agents that cause hand, foot, and mouth disease (HFMD); periodic large epidemics have occurred in recent decades, and it has become a severe public health problem [3,4,5,6,7,8,9]
1998 in mainland China, there have been no reports of the development and use of a lethal animal model employing primary EV-A71 isolates
Summary
Circulating enterovirus 71 (EV-A71)-associated hand, foot, and mouth disease is on the rise in the Asian-Pacific region. Human enterovirus 71 (EV-A71) is a non-enveloped, single-stranded positive-sense RNA virus that belongs to the Enterovirus species A genogroup in the Picornaviridae family. It began circulating in the Netherlands as early as 1963 and was first described in the USA in 1969 [1, 2]. EV-A71 and Coxsackievirus A16 (CV-A16) are the two major etiological agents that cause hand, foot, and mouth disease (HFMD); periodic large epidemics have occurred in recent decades, and it has become a severe public health problem [3,4,5,6,7,8,9]. In mainland China in 1998-2011, all the strains were clustered in the C4 subgenotype of EV-A71
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