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Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for
Mei-Liang Huang1, Pai-Shan Chiang, Min-Yuan Chia
1National Health Research Institutes (NHRI), Zhunan, Taiwan.
Insights
Enterovirus 71 (EV71) genogroups B and C show lower neutralizing antibodies against genogroup A. Specific amino acid signatures in EV71 VP1 and VP2 proteins may explain these antigenic variations, aiding surveillance and vaccine development.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Enterovirus 71 (EV71) outbreaks cause severe neurological and cardiopulmonary issues in children.
- EV71 exhibits diverse genotypes within genogroups A, B, and C, with varying epidemic prevalence in Taiwan.
- Understanding antigenic variations is crucial for controlling EV71 spread.
Purpose of the Study:
- To investigate cross-reactive neutralizing antibody titers against different EV71 genotypes.
- To identify potential molecular markers associated with antigenic variations among EV71 genogroups.
Main Methods:
- Collected historical sera from EV71-infected children across multiple years.
- Measured cross-neutralizing antibody titers against all 11 EV71 genotypes.
- Aligned and compared amino acid sequences of EV71 P1 proteins.
Main Results:
- Children infected with EV71 genogroups B and C exhibited significantly lower neutralizing antibody titers against genogroup A.
- Five specific amino acid signatures in VP1 and VP2 proteins were identified as unique to genogroup A.
- These signatures are potentially linked to the observed antigenic differences between EV71 genogroups.
Conclusions:
- Documented significant antigenic variations among EV71 genogroups.
- Identified key amino acid positions (N143D in VP2; K18R, H116Y, D167E, S275A in VP1) potentially driving these variations.
- Recommended monitoring these specific amino acid sites for EV71 surveillance and vaccine design.
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.
