Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development

  • Huang M
  • Chiang P
  • Chia M
 et al. 
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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 approximately B5 and C1 approximately 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.

Author-supplied keywords

  • Amino Acid
  • Antibodies
  • Child
  • Cross Reactions
  • DNA
  • Enterovirus A
  • Enterovirus Infections
  • Enterovirus Infections: immunology
  • Genotype
  • Human
  • Human: classification
  • Human: genetics
  • Human: immunology
  • Humans
  • Molecular Sequence Data
  • Neutralizing
  • Neutralizing: blood
  • Preschool
  • RNA
  • Sequence Analysis
  • Sequence Homology
  • Taiwan
  • Viral
  • Viral Proteins
  • Viral Proteins: genetics
  • Viral Vaccines
  • Viral Vaccines: immunology
  • Viral: blood
  • Viral: genetics

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  • Mei-Liang L Huang

  • Pai-Shan S Chiang

  • Min-Yuan Y Chia

  • Shu-Ting T Luo

  • Luan-Yin Y Chang

  • Tzou-Yien Y Lin

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