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. 2015 Feb;22(2):221-8.
doi: 10.1128/CVI.00516-14. Epub 2014 Dec 24.

Experimental human infection with Norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity

Rita Czakó  1 , Robert L Atmar  2 , Antone R Opekun  3 , Mark A Gilger  4 , David Y Graham  5 , Mary K Estes  6
Affiliations

Experimental human infection with Norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity

Rita Czakó et al. Clin Vaccine Immunol. 2015 Feb.

Abstract

The human noroviruses (NoVs) are genetically diverse, rapidly evolving RNA viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.

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Figures

FIG 1
FIG 1
Patterns of heterotypic seroresponse vary among individuals (n = 18) challenged with Norwalk virus (a), independent of total preexisting NoV-reactive antibody in serum (b). Values shown in panel a represent seroresponse outcomes for each Norwalk virus-infected individual (n = 18). A seroresponse (black box) is defined as a 4-fold or greater increase between prechallenge and peak BT50 of serum antibody reactive to a particular NoV antigen. Values shown in panel b represent the geometric mean titers of total preexisting homotypic antibody measured by serum ELISA of heterotypic seroresponders (gray boxes; n = 9) compared to narrow heterotypic responders (white boxes; n = 9) at three time points relative to Norwalk virus challenge. Broad heterotypic seroresponders are defined as individuals who developed a blocking antibody seroresponse to 2 or more heterotypic antigens. Narrow heterotypic seroresponders are defined as individuals who developed a blocking antibody seroresponse to 0 or 1 heterotypic antigen. Error bars represent 95% confidence intervals of geometric mean titers. Geometric mean titers between broad and narrow heterotypic seroresponders were compared using the Mann-Whitney U test at each time point; the differences between the geometric mean titers were not statistically significant at any time point.
FIG 2
FIG 2
Relationship between preexisting HBGA-blocking antibody and seroresponse outcome for homotypic (a) and heterotypic (b to e) human NoVs, by individual. Values shown across the top of each panel represent the arithmetic fold increase between prechallenge and peak antigen-specific blocking antibody titer and correspond to the values shown in the stacked bar graph below. Values shown in the lower portion of each panel represent the BT50, or the endpoint serum dilution at which 50% of NoV VLP binding to HBGA was blocked, at prechallenge (white bars) and peak titer (gray or black bars). Seroresponders to each antigen are defined as individuals who developed a 4-fold or greater increase in BT50 against that antigen (black bars), and nonresponders are those who did not (gray bars).
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References

    1. Hall AJ. 2012. Noroviruses: the perfect human pathogens? J Infect Dis 205:1622–1624. doi:10.1093/infdis/jis251. - DOI - PMC - PubMed
    1. Ramani S, Atmar RL, Estes MK. 2014. Epidemiology of human noroviruses and updates on vaccine development. Curr Opin Gastroenterol 30:25–33. doi:10.1097/MOG.0000000000000022. - DOI - PMC - PubMed
    1. Kroneman A, Vega E, Vennema H, Vinjé J, White PA, Hansman G, Green K, Martella V, Katayama K, Koopmans M. 2013. Proposal for a unified norovirus nomenclature and genotyping. Arch Virol 158:2059–2068. doi:10.1007/s00705-013-1708-5. - DOI - PMC - PubMed
    1. Van Beek J, Ambert-Balay K, Botteldoorn N, Eden JS, Fonager J, Hewitt J, Iritani N, Kroneman A, Vennema H, Vinjé J, White PA, Koopmans M. 2013. Indications for worldwide increased norovirus activity associated with emergence of a new variant of genotype II.4, late 2012. Euro Surveill 18:8–9. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20345. - PubMed
    1. Giammanco GM, De Grazia S, Terio V, Lanave G, Catella C, Bonura F, Saporito L, Medici MC, Tummolo F, Calderaro A, Bányai K, Hansman G, Martella V. 2014. Analysis of early strains of the norovirus pandemic variant GII.4 Sydney 2012 identifies mutations in adaptive sites of the capsid protein. Virology 450–451:355–358. doi:10.1016/j.virol.2013.12.007. - DOI - PubMed

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