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

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

Journal of Virology, June 2017

28468886

Sumit Sharma, Beatrice Carlsson, Rita Czakó, Sirkka Vene, Mats Haglund, Johnny Ludvigsson, Göran Larson, Lennart Hammarström, Stanislav V. Sosnovtsev, Robert L. Atmar, Kim Y. Green, Mary K. Estes, Lennart Svensson

The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby 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 last 4 decades.In total 268 sera were investigated for blocking titers (BT50 values) of virus-like particles (VLPs) to pig gastric mucin (PGM) using 4 VLPs that represent different GII.4 norovirus variants identified between 1987-2012.Pre- and post-pandemic sera (sera collected before- and after- isolation of reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1996) and Houston (2002) but not the Sydney (2012) strain to PGM. No statistically significant difference in virus blocking titer was observed between pre- and post-pandemic 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 (GMT 1704) were found among IgA-deficient individuals in comparison to healthy blood donors (GMT 90.9) (p<0.0001). The observation that pre-pandemic sera possess robust virus blocking capacity to viruses identified decades later suggests a common attachment factor at least until year 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 (HBGA), in saliva and gut recognize NoV and are the proposed ligands to facilitate infection. Polymorphisms in HBGA genes and particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII.4 NoV. Emergence of new pandemic GII.4 strains occurs with several years intervals and is proposed to be attributed 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 pre-pandemic sera possess robust virus blocking capacity to viruses identified several decades later. We also show that sera 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.