PMID- 35137154
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20240214
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 226
IP  - 10
DP  - 2022 Nov 11
TI  - Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum.
PG  - 1771-1780
LID - 10.1093/infdis/jiac045 [doi]
AB  - 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 x 104 to 1.2 x 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 x 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.
CI  - (c) 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.
FAU - Rouphael, Nadine
AU  - Rouphael N
AUID- ORCID: 0000-0002-2512-7919
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Beck, Allison
AU  - Beck A
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Kirby, Amy E
AU  - Kirby AE
AD  - Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
FAU - Liu, Pengbo
AU  - Liu P
AD  - Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
FAU - Natrajan, Muktha S
AU  - Natrajan MS
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Lai, Lilin
AU  - Lai L
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Phadke, Varun
AU  - Phadke V
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Winston, Juton
AU  - Winston J
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Raabe, Vanessa
AU  - Raabe V
AUID- ORCID: 0000-0003-2579-1104
AD  - New York University Grossman School of Medicine and New York University Vaccine 
      Center, New York, New York, USA.
FAU - Collins, Matthew H
AU  - Collins MH
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Girmay, Tigisty
AU  - Girmay T
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Alvarez, Alicarmen
AU  - Alvarez A
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Beydoun, Nour
AU  - Beydoun N
AUID- ORCID: 0000-0002-9685-7310
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Karmali, Vinit
AU  - Karmali V
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Altieri-Rivera, Joanne
AU  - Altieri-Rivera J
AD  - Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, 
      Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, 
      USA.
FAU - Lindesmith, Lisa C
AU  - Lindesmith LC
AD  - Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA.
FAU - Anderson, Evan J
AU  - Anderson EJ
AUID- ORCID: 0000-0002-1576-4420
AD  - Division of Infectious Diseases, Department of Pediatrics, School of Medicine, 
      Emory University, Atlanta, Georgia, USA.
FAU - Wang, Yuke
AU  - Wang Y
AD  - Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
FAU - El-Khorazaty, Jill
AU  - El-Khorazaty J
AD  - The Emmes Company, LLC, Rockville, Maryland, USA.
FAU - Petrie, Carey
AU  - Petrie C
AD  - The Emmes Company, LLC, Rockville, Maryland, USA.
FAU - Baric, Ralph S
AU  - Baric RS
AD  - Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA.
FAU - Baqar, Shahida
AU  - Baqar S
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Moe, Christine L
AU  - Moe CL
AD  - Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
FAU - Mulligan, Mark J
AU  - Mulligan MJ
AD  - New York University Grossman School of Medicine and New York University Vaccine 
      Center, New York, New York, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02473224
GR  - R38 AI140299/AI/NIAID NIH HHS/United States
GR  - UL1 TR002378/TR/NCATS NIH HHS/United States
GR  - HHSN272200800005C HHSN272201300018I/NH/NIH HHS/United States
GR  - R01 AI148260/AI/NIAID NIH HHS/United States
GR  - T32AI074492/AI/NIAID NIH HHS/United States
GR  - 203268/Z/16/Z/WT_/Wellcome Trust/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - UL1TR002378/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Norovirus/genetics
MH  - *Caliciviridae Infections
MH  - *Gastroenteritis
MH  - Diarrhea
MH  - Genotype
MH  - Immunoglobulin G
PMC - PMC9650503
OTO - NOTNLM
OT  - ID50
OT  - Snow Mountain virus
OT  - human challenge
OT  - infectious dose
OT  - norovirus
OT  - viral gastroenteritis
COIS- 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.
EDAT- 2022/02/10 06:00
MHDA- 2022/11/15 06:00
PMCR- 2023/02/08
CRDT- 2022/02/09 06:00
PHST- 2021/10/02 00:00 [received]
PHST- 2022/02/03 00:00 [accepted]
PHST- 2022/02/10 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/02/09 06:00 [entrez]
PHST- 2023/02/08 00:00 [pmc-release]
AID - 6524624 [pii]
AID - jiac045 [pii]
AID - 10.1093/infdis/jiac045 [doi]
PST - ppublish
SO  - J Infect Dis. 2022 Nov 11;226(10):1771-1780. doi: 10.1093/infdis/jiac045.