Strain-dependent neutralization reveals antigenic variation of human parechovirus 3

Eveliina Karelehto,Shabih Shakeel,Menno De Jong,Gerrit Koen,Hetty Van Eijk,James A Geraets,Lonneke Van Der Linden,Sabine Van Der Sanden,Dionne Hoogendoorn,Dasja Pajkrt,Aušra Domanska,Katja C Wolthers,Tim Beaumont,Sarah J Butcher

doi:10.1038/s41598-017-12458-5

Abstract

Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015. The rabbit antiserum neutralized all HPeV3 isolates whereas the neutralization capacity of the IVIG batches varied, and the mAb exclusively neutralized the A308/99 strain. Mapping of the amino acid variation among a subset of the HPeV3 strains on an HPeV3 capsid structure revealed that the majority of the surface-exposed amino acid variation was located in the VP1. Furthermore, amino acid mutations in a mAb AT12-015-resistant HPeV3 A308/99 variant indicated the location for potential antigenic determinants. Virus aggregation and the observed antigenic diversity in HPeV3 can explain the varying levels of nAb seropositivity reported in previous studies.

Highlights

Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide
To study antigenic diversity of HPeV3, we determined the neutralizing activity of the rabbit HPeV3 hyperimmune polyclonal serum, an HPeV3-specific human monoclonal antibody (mAb) AT12015, and Dutch and Japanese intravenous immunoglobulin (IVIG) batches against a panel of chloroform-treated HPeV3 isolates
In this study we described antigenic diversity of HPeV3 strains isolated in various geographical locations and years

Summary

Introduction

Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. The observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015. For HPeV1, neutralization rates above 90% have been reported in adults in Finland, the Netherlands and in Japan[15,18,19] These high rates suggest that young children are likely protected against HPeV1 infection by maternal antibodies, while low prevalence of HPeV3-specific nAbs in the adult population could explain the higher rates of HPeV3-related severe illness in neonates and infants. To understand the genetic basis of the antigenic variation and to identify potentially immunogenic sites, we sequenced the capsid-encoding regions of 10 HPeV3 isolates, generated an AT12-015-resistant (MAR) HPeV3 variant and mapped the observed amino acid variation on the virus capsid structure

Methods

Results

Conclusion