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

• Published in: The Journal of infectious diseases Vol. 226; no. 10; pp. 1771 - 1780
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 11.11.2022
• Subjects: Adult; Blood groups; Caliciviridae Infections; Clinical trials; Diarrhea; Gastroenteritis; Genotype; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Infections; Inoculum; Major; Norovirus; Norovirus - genetics; Seroconversion; viral gastroenteritis; ID; Snow Mountain virus; norovirus; infectious dose; human challenge; ID50
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiac045

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. Clinical Trials Registration NCT02473224. We evaluated the use of a new GII.2 inoculum in a human challenge that could facilitate the evaluation of norovirus vaccines and therapeutics and observed high rates of infection and illness in both secretor-positive and -negative subjects.