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

Autor:	Rouphael N; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Beck A; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Kirby AE; Rollins School of Public Health, Emory University, Atlanta, Georgia, USA., Liu P; Rollins School of Public Health, Emory University, Atlanta, Georgia, USA., Natrajan MS; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Lai L; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Phadke V; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Winston J; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Raabe V; New York University Grossman School of Medicine and New York University Vaccine Center, New York, New York, USA., Collins MH; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Girmay T; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Alvarez A; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Beydoun N; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Karmali V; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Altieri-Rivera J; Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA., Lindesmith LC; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Anderson EJ; Division of Infectious Diseases, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA., Wang Y; Rollins School of Public Health, Emory University, Atlanta, Georgia, USA., El-Khorazaty J; The Emmes Company, LLC, Rockville, Maryland, USA., Petrie C; The Emmes Company, LLC, Rockville, Maryland, USA., Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Baqar S; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Moe CL; Rollins School of Public Health, Emory University, Atlanta, Georgia, USA., Mulligan MJ; New York University Grossman School of Medicine and New York University Vaccine Center, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2022 Nov 11; Vol. 226 (10), pp. 1771-1780.
DOI:	10.1093/infdis/jiac045
Abstrakt:	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. Competing Interests: Potential conflicts of interest. N. R. has research support from Merck, Sanofi Pasteur, Lilly, Quidel, Pfizer and do not pose a conflict of interest for this paper. M. J. M. has research support from Lilly, Pfizer, Sanofi; personal fees from Pfizer and Meissa Vaccines and do not pose a conflict of interest for this paper. L. C. L. and R. S. B. have ongoing collaborations with Hillvax, VaxArt and Takeda that are unrelated and do not pose conflicts of interest with this report. C.L.M has collaborations with Takeda that are unrelated and do not pose conflicts of interest with this report. V. R. has research support from Sanofi Pasteur, unrelated, no conflict of interest with this report. E. J. A. has consulted for Pfizer, Sanofi Pasteur, Janssen, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He also serves on a safety monitoring board for Kentucky BioProcessing, Inc. and Sanofi Pasteur. No conflict of interest with this report. C. P., J. E. K., A. E. K., A. B., P. L., M. S. N., L. L., V. P., J. W., M. H. C., T. G., A. A., N. B., V. K., J. A. R., Y. W., and S. B. have no competing interests to declare. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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