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Viruses 2019, 11(2), 91; https://doi.org/10.3390/v11020091

Immunological Cross-Reactivity of an Ancestral and the Most Recent Pandemic Norovirus GII.4 Variant

Vaccine Research Center, Faculty of Medicine and Health Technology, Tampere University, Biokatu 10, FI-33520 Tampere, Finland
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Received: 19 December 2018 / Revised: 11 January 2019 / Accepted: 18 January 2019 / Published: 22 January 2019
(This article belongs to the Special Issue Noroviruses)
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Abstract

Norovirus (NoV) genotype GII.4 is responsible for the majority of NoV infections causing pandemics every few years. A NoV virus-like particle (VLP)-based vaccine should optimally cover the high antigenic variation within the GII.4 genotype. We compared the immune responses generated by VLPs of the ancestral GII.4 1999 strain (GII.4 1995/96 US variant) and the most recent GII.4 Sydney 2012 pandemic strains in mice. No significant differences were observed in the type-specific responses but GII.4 1999 VLPs were more potent in inducing high-avidity antibodies with better cross-reactivity. GII.4 1999 immune sera blocked binding of GII.4 2006 and GII.4 2012 VLPs to the putative receptors in a surrogate neutralization assay, whereas GII.4 2012 immune sera only had low blocking activity against GII.4 2006 VLPs. Amino acid substitution in the NERK motif (amino acids 310, 316, 484, and 493, respectively), altering the access to conserved blocking epitope F, moderately improved the cross-blocking responses against mutated GII.4 2012 VLPs (D310N). NoV GII.4 1999 VLPs, uptaken and processed by antigen-presenting cells, induced stronger interferon gamma (IFN-γ) production from mice splenocytes than GII.4 2012 VLPs. These results support the use of GII.4 1999 VLPs as a major component of a NoV vaccine. View Full-Text
Keywords: norovirus; ancestor; variant; GII.4; immune responses; cross-reactivity; blocking antibodies; NERK motif norovirus; ancestor; variant; GII.4; immune responses; cross-reactivity; blocking antibodies; NERK motif
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Tamminen, K.; Malm, M.; Vesikari, T.; Blazevic, V. Immunological Cross-Reactivity of an Ancestral and the Most Recent Pandemic Norovirus GII.4 Variant. Viruses 2019, 11, 91.

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