Monitoring Antigenic Variations of Enterovirus 71: Implications for Virus Surveillance and Vaccine Development

Abstract

Enterovirus 71 (EV71) causes life-threatening epidemics in Asia and can be phylogenetically classified into three major genogroups (A∼C) including 11 genotypes (A, B1∼B5, and C1∼C5). Recently, EV71 epidemics occurred cyclically in Taiwan with different genotypes. In recent years, human studies using post-infection sera obtained from children have detected antigenic variations among different EV71 strains. Therefore, surveillance of enterovirus 71 should include phylogenetic and antigenic analysis. Due to limitation of sera available from children with EV71 primary infection, suitable animal models should be developed to generate a panel of antisera for monitoring EV71 antigenic variations. Twelve reference strains representing the 11 EV71 genotypes were grown in rhabdomyosarcoma cells. Infectious EV71 particles were purified and collected to immunize rabbits. The rabbit antisera were then employed to measure neutralizing antibody titers against the 12 reference strains and 5 recent strains. Rabbits immunized with genogroup B and C viruses consistently have a lower neutralizing antibody titers against genogroup A (≧8-fold difference) and antigenic variations between genogroup B and C viruses can be detected but did not have a clear pattern, which are consistent with previous human studies. Comparison between human and rabbit neutralizing antibody profiles, the results showed that ≧8-fold difference in rabbit cross-reactive antibody ratios could be used to screen EV71 isolates for identifying potential antigenic variants. In conclusion, a rabbit model was developed to monitor antigenic variations of EV71, which are critical to select vaccine strains and predict epidemics.

A Molecular Approach Applied to Enteroviruses Surveillance in Northern Taiwan, 2008-2012

“…EV71 seems to evolve quicker in the past 15 years and different EV71 genotypes have caused large-scale epidemics in tropical and subtropical Asia since 1997. Moreover, antigenic variations among different genotypes were observed based on serum neutralization test using rabbit and human antisera [23–27]. Based on the VP1-CODEHOP test, we found that multiple EV71 genotypes co-circulated in 2008–2012 but EV71 sub-genotypes B5b and B5c caused large-scale epidemics in 2008 and 2012, respectively, which are consistent with other studies analyzing full VP1 sequences and complete genomes [24, 27].…”

Evaluation of MDCK Cell-Derived Influenza H7N9 Vaccine Candidates in Ferrets

“…Viral particles were deposited on a carbon-coated 200 mesh copper grid for 1 min at room temperature and then the copper grid was stained with 2% phosphotungstic acid solution for 1 min. The stained grid was dried for 1 day at room temperature and observed under a JEM 1200EX transmission electron microscopy [ 23 ].…”

Evolution, antigenicity and pathogenicity of global porcine epidemic diarrhea virus strains

“…In addition to inferring the antigenicity by sequence data Sun et al, 2013), expression of recombinant proteins in eukaryotic systems and generating antiserum and/or MAbs in laboratory animals could be alternative methods to explore the antigenic variations among PEDV strains . However, whether the structure of recombinant proteins reflects the proteins in the intact virus (Makadiya et al, 2016), or whether cross-reactive neutralizing antibody profiles defined using antisera from injected small laboratory animals are similar to those observed using post-infection sera obtained from their natural host in the field needs to be confirmed (Chia et al, 2014).…”

“…Multiple datasets of the serological assays from different laboratories worldwide could be combined for constructing a comprehensive PEDV antigenic cartography by a computational framework approach (Cai et al, 2010;Smith et al, 2004). Subsequently, a similar approach was also applied for other RNA viruses with high antigenic variation, such as human enteroviruses (Chia et al, 2014) and noroviruses (Debbink Fig. 4.…”