> Details

Rouphael, Nadine; Beck, Allison; Kirby, Amy E; Liu, Pengbo; Natrajan, Muktha S; Lai, Lilin; Phadke, Varun; Winston, Juton; Raabe, Vanessa; Collins, Matthew H; Girmay, Tigisty; Alvarez, Alicarmen; Beydoun, Nour; Karmali, Vinit; Altieri-Rivera, Joanne; Lindesmith, Lisa C; Anderson, Evan J; Wang, Yuke; El-Khorazaty, Jill; Petrie, Carey; Baric, Ralph S; Baqar, Shahida; Moe, Christine L; Mulligan, Mark J

Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum

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  • Media type: E-Article
  • Title: Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum
  • Contributor: Rouphael, Nadine; Beck, Allison; Kirby, Amy E; Liu, Pengbo; Natrajan, Muktha S; Lai, Lilin; Phadke, Varun; Winston, Juton; Raabe, Vanessa; Collins, Matthew H; Girmay, Tigisty; Alvarez, Alicarmen; Beydoun, Nour; Karmali, Vinit; Altieri-Rivera, Joanne; Lindesmith, Lisa C; Anderson, Evan J; Wang, Yuke; El-Khorazaty, Jill; Petrie, Carey; Baric, Ralph S; Baqar, Shahida; Moe, Christine L; Mulligan, Mark J
  • imprint: Oxford University Press (OUP), 2022
  • Published in: The Journal of Infectious Diseases
  • Language: English
  • DOI: 10.1093/infdis/jiac045
  • ISSN: 0022-1899; 1537-6613
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trials Registration</jats:title> <jats:p>NCT02473224.</jats:p> </jats:sec>
  • Access State: Open Access