BackgroundRecently, enterovirus 71 (EV71) has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C) and 11 genotypes (A, B1∼B5 and C1∼C5). In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2), 2000–2001 (B4), 2004–2005 (C4), and 2008 (B5). In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes.MethodsWe collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses.ResultsSerology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (>4-fold difference). The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1) are specific for genogroup A and may be related to the observed antigenic variations.ConclusionsThis study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions.

The 2008 nationwide EV71 epidemic was caused by genotype B5 that was likely introduced to Taiwan from Southeast Asia. Clinical features of the 2008 epidemic were not different from those observed before in Taiwan. Potential antigenic variations between genotype C4 and B5 viruses could be detected and its long-term epidemiologic significance needs further investigation to clarify.

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Enterovirus 71 (EV71) was first described in USA in 1969 but retrospective studies in The Netherlands further detected EV71 in the clinical specimens collected in 1963. EV71 has one single serotype measured by using hyperimmune animal antisera but can be phylogenetically classified into three genogroups (A, B, and C) including 11 genotypes (A, B1-B5, C1-C5). In Taiwan, EV71 caused a large-scale nationwide epidemic in 1998. Retrospective studies further detected EV71 in clinical specimens collected from hand-foot-mouth disease patients in 1980 and 1986. Therefore, EV71 may have circulated in Taiwan prior to 1980. Since 1998, EV71 has cyclically caused nationwide epidemics with different predominant genotypes in 1998 (genotype C2), 2000-2001 (B4), 2005 (C4), 2008 (B5), and 2012 (B5). Phylogenetic analysis revealed that C4 viruses isolated in 2005 were probably from China, B5 viruses isolated in 2008 were probably from South Eastern Asia, and B5 viruses isolated in 2012 were probably from Xiamen, China. Several studies have collected postinfection sera from children to measure cross-reactive neutralizing antibody titers against different EV71 genotypes and found that antigenic differences between genogroup B and C viruses did not have a clear pattern but that genotype A virus was antigenically different from genogroup B and C viruses. In conclusion, EV71 cyclically caused nationwide epidemics through international importations. EV71 surveillance in Taiwan should combine genetic and serological methods.

Enterovirus 71 (EV71) causes life-threatening disease outbreaks in young children in Asia. This cohort study was conducted to understand the dynamics of maternal EV71 antibodies in Taiwanese young infants. Approximately 50% of neonates had detectable EV71 neutralizing antibodies, which declined to almost undetectable levels by 6 months of age.