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J Infect Dis. 2015 Mar 15;211(6):870-8. doi: 10.1093/infdis/jiu497. Epub 2014 Sep 9.

Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults.

Author information

1
Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio.
2
Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
3
Emory University School of Medicine, Atlanta, Georgia.
4
University of Rochester Medical Center, New York.
5
University of Maryland School of Medicine, Baltimore.
6
Centers for Disease Control and Prevention.
7
Emory University Rollins School of Public Health, Atlanta, Georgia.
8
Shin Nippon Biomedical Laboratories, Baltimore.
9
The EMMES Corp, Rockville, Maryland.
10
Takeda Vaccines Inc, Deerfield, Illinois.
11
Takeda Pharmaceuticals International, Zurich, Switzerland.

Abstract

BACKGROUND:

Vaccines against norovirus, the leading cause of acute gastroenteritis, should protect against medically significant illness and reduce transmission.

METHODS:

In this randomized, double-blind, placebo-controlled trial, 18- to 50-year-olds received 2 injections of placebo or norovirus GI.1/GII.4 bivalent vaccine-like particle (VLP) vaccine with 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and alum. Participants were challenged as inpatients with GII.4 virus (4400 reverse transcription polymerase chain reaction [RT-PCR] units), and monitored for illness and infection.

RESULTS:

Per protocol, 27 of 50 (54.0%) vaccinees and 30 of 48 (62.5%) controls were infected. Using predefined illness and infection definitions, vaccination did not meet the primary endpoint, but self-reported cases of severe (0% vaccinees vs. 8.3% controls; P = .054), moderate or greater (6.0% vs. 18.8%; P = .068), and mild or greater severity of vomiting and/or diarrhea (20.0% vs. 37.5%; P = .074) were less frequent. Vaccination also reduced the modified Vesikari score from 7.3 to 4.5 (P = .002). Difficulties encountered were low norovirus disease rate, and inability to define illness by quantitative RT-PCR or further antibody rise in vaccinees due to high vaccine-induced titers. By day 10, 11 of 49 (22.4%) vaccinees were shedding virus compared with 17 of 47 (36.2%) placebo recipients (P = .179).

CONCLUSIONS:

Bivalent norovirus VLP vaccine reduced norovirus-related vomiting and/or diarrhea; field efficacy studies are planned. Clinical Trials Registration. NCT01609257.

KEYWORDS:

acute gastroenteritis; challenge; norovirus; vaccine

Comment in

PMID:
25210140
PMCID:
PMC5914500
DOI:
10.1093/infdis/jiu497
[Indexed for MEDLINE]
Free PMC Article

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