{"doi":"10.1093/infdis/jiac045","title":"Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum","abstract":"BACKGROUND: Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis. We evaluated the use of a new GII.2 inoculum in a human challenge. METHODS: Forty-four healthy adults (36 secretor-positive and 8 secretor-negative for histo-blood group antigens) were challenged with ascending doses of a new safety-tested Snow Mountain virus (SMV) GII.2 norovirus inoculum (1.2 × 104 to 1.2 × 107 genome equivalent copies [GEC]; n = 38) or placebo (n = 6). Illness was defined as diarrhea and/or vomiting postchallenge in subjects with evidence of infection (defined as GII.2 norovirus RNA detection in stool and/or anti-SMV immunoglobulin G [IgG] seroconversion). RESULTS: The highest dose was associated with SMV infection in 90%, and illness in 70% of subjects with 10 of 12 secretor-positive (83%) and 4 of 8 secretor-negative (50%) becoming ill. There was no association between prechallenge anti-SMV serum IgG concentration, carbohydrate-binding blockade antibody, or salivary immunoglobulin A and infection. The median infectious dose (ID50) was 5.1 × 105 GEC. CONCLUSIONS: High rates of infection and illness were observed in both secretor-positive and secretor-negative subjects in this challenge study. However, a high dose will be required to achieve the target of 75% illness to make this an efficient model for evaluating potential norovirus vaccines and therapeutics. 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Altieri-Rivera","orcid":null,"position":14,"is_corresponding":false},{"id":298000,"name":"Lisa C. Lindesmith","orcid":"0000-0001-9567-0522","position":15,"is_corresponding":false},{"id":94484,"name":"Evan J. Anderson","orcid":"0000-0002-1576-4420","position":16,"is_corresponding":false},{"id":934841,"name":"Yuke Wang","orcid":"0000-0002-9615-7859","position":17,"is_corresponding":false},{"id":853216,"name":"Jill El-Khorazaty","orcid":"0000-0003-2719-0767","position":18,"is_corresponding":false},{"id":494891,"name":"Carey R. Petrie","orcid":null,"position":19,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":20,"is_corresponding":false},{"id":633783,"name":"Shahida Baqar","orcid":null,"position":21,"is_corresponding":false},{"id":541214,"name":"Christine L. Moe","orcid":"0000-0003-3628-1783","position":22,"is_corresponding":false},{"id":3883,"name":"Mark J. 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