Can we trust non-polio enterovirus sero-surveillance? Evaluation of cross-neutralisation between enteroviruses

Enteroviruses (EV) are worldwide circulating viruses causing a broad range of disease manifestations. Sero-surveillance, by measuring neutralising antibodies against specific EV types, can provide valuable information on viral spread and community circulation. EV neutralisation is generally regarded as type-specific, providing the foundation for the reliability of EV sero-surveillance. Recent data has challenged the assumption of type-specific neutralisation. To study the extent of cross-neutralisation, we measured neutralising antibody titres in EV type-specific polyclonal animal sera against twelve recently circulating homotypic and heterotypic clinical and prototype strains belonging to all four EV species, making use of virus neutralisation assays. We found no cross-neutralising Abs against EV-A71, CVA4, CVB2, CVB5, CVA24, and EV-D68. No cross-neutralising antibodies were found in poliovirus 1, 2 and 3 anti-sera. However, cross-neutralising antibodies were found in anti-CVA20 and anti-CVA24 animal sera against the included echovirus types, E11 and E30. Our study demonstrates that cross-neutralisation among EV is generally uncommon, though not absent. To enhance the reliability and comparability of sero-surveillance studies, cross-neutralisation between geno- and subgenotypes should be further evaluated in humans and virus neutralisation assays (VNA) should be further standardised.