1400. Human challenge model using a norovirus  GII.4 strain: susceptility to infection
Session: Oral Abstract Session: Host Susceptibility to Viral Infections
Sunday, October 23, 2011: 8:15 AM
Room: 156ABC
Background: Noroviruses are recognized as the most important cause of non-bacterial epidemics of acute gastroenteritis worldwide with GII.4 strains causing the majority of current infections. Further, it has been recently recognized that noroviruses recognize human histo-blood group antigens as receptors. We therefore developed a human challenge model using a GII.4 strain and  evaluated the role of secretor status in susceptibility to the challenge strain

Methods: Forty healthy adults (23 secretor positive (secretors) and 17 secretor negative (non-secretor)) with low antibody titers to the challenge strain were challenged with 104 PCR genome units of a new GII.4 strain.  Subjects were followed for 5 days in our challenge unit and assessed daily for fever, diarrhea , vomiting and other signs of illness.  Stools were collected up to three times daily and assessed for norovirus shedding by PCR.

Results: Of the 23 secretor subjects 14 (61%) shed virus, 13 (57%) became ill ( vomiting and /or diarrhea) and 52% seroconverted ( 4 fold increase in GIi.4 antibody).  In comparison only one of the 17 non-secretors became ill and one other shed virus for a single day ( P<0.001 for each variable) .  Illness in both secretors and non-secretors was mild to moderate in severity and lasted 1-3 days.

Conclusion: Secretor status determined the susceptibility to a norovirus GII.4 challenge.  This human challenge model should be useful for evaluating norovirus vaccines and antivirals.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Robert Frenck, MD, David Bernstein, MD, Ming Xia, PhD, Pengwei Huang, MD, Weiming Zhong, Susan Parker, RN, Monica McNeal, MS, Michelle Dickey, CNP and Xi Jiang, PhD, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Disclosures:

R. Frenck, Pfizer: Investigator, Research support

D. Bernstein, None

M. Xia, None

P. Huang, None

W. Zhong, None

S. Parker, None

M. McNeal, None

M. Dickey, None

X. Jiang, None

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