Challenges to Licensure of Enterovirus 71 Vaccines

Enteroviruses (EVs) are single-stranded, positive-sense RNA viruses in the Picornaviridae family. They cause various clinical manifestations, including cutaneous, visceral, and neurological diseases [1]. There are more than 100 human enterovirus serotypes, including 3 poliovirus serotypes, 23 coxsackievirus A (CA) serotypes, 6 coxsackievirus B (CB) serotypes, 31 echovirus serotypes, and 39 numbered enterovirus serotypes (EV68-71, EV73-102, EV104-107, and EV109). Human enteroviruses can be phylogenetically classified into four species (A, B, C, and D) [1,2]. For many years polioviruses were the most important enteroviruses since they caused large outbreaks of paralytic disease before poliovirus vaccines were available. Although EV71 was first isolated in 1969, a retrospective analysis shows that this virus circulated in the Netherlands as early as 1963. Recent molecular evolution studies predicted that EV71 could emerge in the human population around 1941 [3,4]. Recently, EV71 repeatedly caused life-threatening outbreaks of hand-foot-mouth disease (HFMD) with neurological complications in Asian children. The neurological manifestations progress very quickly and range from aseptic meningitis to acute flaccid paralysis and brainstem encephalitis [2]. Due to its tremendous impact on healthcare systems, development of EV71 vaccines is a national priority in some Asian countries. Vaccine candidates are being evaluated in humans. Several review articles related to EV71 epidemiology, clinical management, pathogenesis, and preclinical vaccine development have been published [1,2,[5] In this review we focus on disease burden of enteroviruses and EV71 in Asian countries, importance of the antigenic and genetic variations, and the potential challenges to licensure and delivery of EV71 vaccines.