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J Virol. 2017 Jun 26;91(14). pii: e00567-17. doi: 10.1128/JVI.00567-17. Print 2017 Jul 15.

Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades.

Author information

1
Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
2
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
3
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
4
Public Health Agency of Sweden, Stockholm, Sweden.
5
Department of Infectious Diseases, County Hospital Kalmar, Kalmar, Sweden.
6
Division of Pediatrics and Diabetes Research Centre, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
7
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
8
Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institute, Stockholm, Sweden.
9
Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
10
Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden lennart.t.svensson@liu.se.
11
Division of Medicine, Karolinska Institute, Stockholm, Sweden.

Abstract

The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII.4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII.4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of ≥160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P < 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII.4 NoV.IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII.4 NoV. The emergence of new pandemic GII.4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.

KEYWORDS:

VLP; norovirus; pandemic

PMID:
28468886
PMCID:
PMC5487561
DOI:
10.1128/JVI.00567-17
[Indexed for MEDLINE]
Free PMC Article

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