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

Publication Type
Journal Article
Year of Publication
2022
Authors
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
Secondary
J Infect Dis
Date Published
2022 Feb 08
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 (1.2x10 4 to 1.2x10 7 genomic equivalent copies [GEC]; n=38) or placebo ( n=6). Illness was defined as diarrhea and/or vomiting post challenge in subjects with evidence of infection (defined as GII.2 norovirus RNA detection in stool and/or anti-SMV 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 pre-challenge anti-SMV serum IgG concentration, carbohydrate-binding blockade antibody, or salivary IgA and infection. The ID50 was 5.1×10 5 GEC.

CONCLUSIONS: High rates of infection and illness were observed in both secretor-positive and 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.