Cross-reactive Neutralizing Antibody Responses to Enterovirus 71 Infections in Young Children: Implications for Vaccine Development

Background: recently,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. methods: we 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. results: serology 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. conclusions: this study documented antigenic variations among different ev71 genogroups and identified potential immunodominant amino acid positions. enterovirus surveillance and vaccine development should monitor these positions. © 2013 huang et al.