Enterovirus 71 Vaccine: When Will it be Available?

Abstract

Enterovirus 71 (EV71) is a positive-sense RNA virus that belongs to the enterovirus genus in the family Picornaviridae along with other important human pathogens, such as polioviruses and rhinoviruses. EV71 was first isolated in l969 in the United States from a child with neurological disease, but a recent retrospective study suggested that EV71 was circulating in the Netherlands as early as 1963.1 To date, there is only one serotype of EV71 as measured by hyperimmune animal antiserum. Phylogenetically, EV71 can be classified into three genogroups (A, B and C) and 11 genotypes (A, B1–B5, and C1–C5) by analyzing the most variable capsid protein sequences (VP1).1 From an evolutionary prospective, a recent analysis of 628 EV71 VP1 sequences estimated that EV71 emerged in the human population at approximately 1941.2 Recombination, which is a common occurrence among enteroviruses, is a likely explanation for the emergence of EV71, but it would require full genomic analysis of EV71 to prove such an evolutionary concept. According to a clinical observation of children acquiring EV71 infection during the 1998 outbreak in Taiwan, severe EV71 infection progresses through four stages: self-limited hand-foot-mouth disease/ herpangina (stage 1), encephalitis or myelitis (stage 2), cardiopulmonary failure (stage 3), and convalescence (stage 4). Young children under 4 years pose a higher risk for severe infections, but the underlying cause for the varied clinical spectrum is not clear.3 While cardiovascular collapse is a terminal event of fatal EV71 infection, the virus is not found in the heart or lung, but only in the nervous system, suggesting that cardiopulmonary collapse is a neurogenic event.3 Although it is continuously circulating in most countries, EV71 has caused several outbreaks sporadically in the 1970s, i.e. 1975 in Bulgaria and 1978 in Hungary. However, in the past decade, EV71 has appeared to cause large outbreaks of neurological infection in several Asian countries with increasing frequency, i.e. 1997 in Malaysia, 1998 in Taiwan, and 2008 in China and multiple Asian countries.3,4 While the reasons for the underlying cause of these outbreaks remain unclear, developing an effective vaccine is perceived as the top priority among the control measures of EV71 in the Asian Pacific region. Based on historical experiences with inactivated poliovirus vaccines (IPV), inactivated EV71