Neutralising Antibodies against Enterovirus and Parechovirus in IVIG Reflect General Circulation: A Tool for Sero-Surveillance

Abstract

Non-polio enteroviruses (NPEV) and parechoviruses (PeV) are widespread pathogens that cause significant morbidity. Surveillance is based on culturing or genotyping of virus strains found in clinical samples. Sero-surveillance, by measuring neutralising antibodies (nAb) through virus neutralisation assays (VNA), could provide additional information as it offers a more comprehensive overview of exposure to circulating types in the general population. In our study we evaluated Intravenous immunoglobulins (IVIG) to generate sero-surveillance data. We performed VNA of nineteen NPEV and PeV with Dutch IVIG batches from two different time points (2010 and 2017) and an IVIG batch from Vietnam (2011). We compared our findings with geno- and sero-surveillance data and evaluated changes over time and between the two countries. Our findings show a good correlation with what is known from geno-surveillance data. The highest nAb titres were found against strains from Enterovirus B, while we did not observe nAb titres against strains belonging to Enterovirus C. In conclusion, we demonstrated that sero-surveillance by means of IVIG can be used to obtain insight into circulation of EV and PeV genotypes. This is of particular interest for public health, to evaluate changes over time and population susceptibility to emerging genotypes.

Keywords: Enterovirus; Parechovirus; sero-surveillance; surveillance; virus neutralisation assay.

Figure 1

Neutralising antibody titres against different Entero- and Parechovirus strains a. Dutch 2017 IVIG batch b. Differences over time between Dutch 2010 and 2017 IVIG batch c. Differences between 2011 Vietnamese and 2010 Dutch IVIG batch. Asterisks (*) indicate a more than twofold difference in nAb titre between IVIG batches. GMT; geometric mean titre, IVIG; intravenous immunoglobulins, nAb titre; neutralising antibody titre, EV; enterovirus, PeV; parechovirus, CVA; coxsackievirus A, CVB; coxsackievirus B, E; echovirus, NL; the Netherlands, Vi; Vietnam.