Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum
2022 Feb 08
Journal Article
Authors:
Rouphael, N.;
Beck, A.;
Kirby, A.E.;
Liu, P.;
Natrajan, M.S.;
Lai, L.;
Phadke, V.;
Winston, J.;
Raabe, V.;
Collins, M.H.;
Girmay, T.;
Alvarez, A.;
Beydoun, N.;
Karmali, V.;
Altieri-Rivera, J.;
Lindesmith, L.C.;
Anderson, E.J.;
Wang, Y.;
El-Khorazaty, J.;
Petrie, C.;
Baric, R.S.;
Baqar, S.;
Moe, C.L.;
Mulligan, M.J.
Secondary:
J Infect Dis
Volume:
226
Pagination:
1771-1780
Issue:
10
PMID:
35137154
URL:
https://pubmed.ncbi.nlm.nih.gov/35137154/
Keywords:
human challenge; Id50; infectious dose; norovirus; Snow Mountain virus; viral gastroenteritis
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.
