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.
RCT Entities:
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.
Authors: Rishi Desai; Christal D Hembree; Andreas Handel; Jonathan E Matthews; Benjamin W Dickey; Sharla McDonald; Aron J Hall; Umesh D Parashar; Juan S Leon; Benjamin Lopman Journal: Clin Infect Dis Date: 2012-04-04 Impact factor: 9.079
Authors: Yang Yang; Ming Xia; Ming Tan; Pengwei Huang; Weiming Zhong; Xiao Li Pang; Bonita E Lee; Jarek Meller; Tao Wang; Xi Jiang Journal: J Virol Date: 2010-06-30 Impact factor: 5.103
Authors: J S Noel; T Ando; J P Leite; K Y Green; K E Dingle; M K Estes; Y Seto; S S Monroe; R I Glass Journal: J Med Virol Date: 1997-12 Impact factor: 2.327
Authors: Gabriel I Parra; Karin Bok; Ross Taylor; Joel R Haynes; Stanislav V Sosnovtsev; Charles Richardson; Kim Y Green Journal: Vaccine Date: 2012-03-31 Impact factor: 3.641
Authors: Lisa C Lindesmith; Martina Beltramello; Eric F Donaldson; Davide Corti; Jesica Swanstrom; Kari Debbink; Antonio Lanzavecchia; Ralph S Baric Journal: PLoS Pathog Date: 2012-05-17 Impact factor: 6.823
Authors: Elaine Scallan; Robert M Hoekstra; Frederick J Angulo; Robert V Tauxe; Marc-Alain Widdowson; Sharon L Roy; Jeffery L Jones; Patricia M Griffin Journal: Emerg Infect Dis Date: 2011-01 Impact factor: 6.883
Authors: Shayla Hesse; Frederick H Neill; Mary K Estes; Sreejesh Shanker; B V Venkataram Prasad; Jennifer Ferreira; Robert L Atmar Journal: Clin Vaccine Immunol Date: 2015-12-09
Authors: Sanghyun Lee; Hejun Liu; Craig B Wilen; Zoi E Sychev; Chandni Desai; Barry L Hykes; Robert C Orchard; Broc T McCune; Ki-Wook Kim; Timothy J Nice; Scott A Handley; Megan T Baldridge; Gaya K Amarasinghe; Herbert W Virgin Journal: Cell Host Microbe Date: 2019-05-23 Impact factor: 21.023
Authors: Anna D Koromyslova; Jessica M Devant; Turgay Kilic; Charles D Sabin; Virginie Malak; Grant S Hansman Journal: J Virol Date: 2020-06-16 Impact factor: 5.103
Authors: Robert L Atmar; David I Bernstein; G Marshall Lyon; John J Treanor; Mohamed S Al-Ibrahim; David Y Graham; Jan Vinjé; Xi Jiang; Nicole Gregoricus; Robert W Frenck; Christine L Moe; Wilbur H Chen; Jennifer Ferreira; Jill Barrett; Antone R Opekun; Mary K Estes; Astrid Borkowski; Frank Baehner; Robert Goodwin; Anthony Edmonds; Paul M Mendelman Journal: Clin Vaccine Immunol Date: 2015-06-03
Authors: Daniel Olson; Molly M Lamb; Maria R Lopez; Maria A Paniagua-Avila; Alma Zacarias; Gabriela Samayoa-Reyes; Celia Cordon-Rosales; Edwin J Asturias Journal: Am J Trop Med Hyg Date: 2017-07-19 Impact factor: 2.345
Authors: M de Graaf; J van Beek; H Vennema; A T Podkolzin; J Hewitt; F Bucardo; K Templeton; J Mans; J Nordgren; G Reuter; M Lynch; L D Rasmussen; N Iritani; M C Chan; V Martella; K Ambert-Balay; J Vinjé; P A White; M P Koopmans Journal: Euro Surveill Date: 2015-07-02