Norovirus Vaccine Against Experimental Human GII.4 Virus Illness: A Challenge Study in Healthy Adults

• Type of Material: Article
• Authors: David I. Bernstein, University of Cincinnati; Robert L. Atmar, Baylor College of Medicine; G Marshall Lyon III, Emory University; John J. Treanor, Rockefeller University; Wilbur H. Chen, University of Maryland; Xi Jiang, University of Cincinnati; Jan Vinje, Centers for Disease Control and Prevention; Nicole Gregoricus, Centers for Disease Control and Prevention; Robert W. Frenck, University of Cincinnati; Christine L Moe, Emory University; Mohamed S. Al-Ibrahim, Shin Nippon Biomedical Laboratories; Jill Barrett, Emmes Corporation; Jennifer Ferreira, Emmes Corporation; Mary K. Estes, Baylor College of Medicine; David Y. Graham, Baylor College of Medicine; Robert Goodwin, Takeda Vaccines Inc.; Astrid Borkowski, Takeda Pharmaceuticals International; Ralf Clemens, Takeda Pharmaceuticals International; Paul M. Mendelman, Takeda Vaccines Inc.
• Language: English
• Date: 2015-03-15
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jiu497
• Title of Journal or Parent Work: Journal of Infectious Diseases
• ISSN: 0022-1899
• Volume: 211
• Issue: 6
• Start Page: 870
• End Page: 878
• Grant/Funding Information: Financial support: This work was entirely supported by Takeda Vaccines, Inc.
• Keywords: OUTBREAKS; Science & Technology; Immunology; vaccine; IMMUNOGENICITY; acute gastroenteritis; UNITED-STATES; PARTICLES; Infectious Diseases; CELLULAR IMMUNE-RESPONSES; MUCOSAL; ACUTE GASTROENTERITIS; VOLUNTEERS; norovirus; CHILDREN; BLOOD GROUP ANTIGENS; Life Sciences & Biomedicine; challenge; Microbiology
• Research Categories: Biology, Microbiology; Biology, Virology; Health Sciences, Immunology

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. Bival ent norovirus VLP vaccine reduced norovirus-related vomiting and/or diarrhea; field efficacy studies are planned.