Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults.
Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults.
复制标题
DOI：
10.1093/infdis/jiu497
复制
发表时间：
2015-03-15
期刊：
影响因子：
--
通讯作者：
Mendelman PM
中科院分区：
文献类型：
--
作者：
Bernstein DI;Atmar RL;Lyon GM;Treanor JJ;Chen WH;Jiang X;Vinjé J;Gregoricus N;Frenck RW Jr;Moe CL;Al-Ibrahim MS;Barrett J;Ferreira J;Estes MK;Graham DY;Goodwin R;Borkowski A;Clemens R;Mendelman PM
诺如病毒是急性胃肠炎的主要原因，针对诺如病毒的疫苗应能预防医学上重要的疾病并减少传播。在这项随机、双盲、安慰剂对照试验中，18至50岁的受试者接受了2次安慰剂或诺如病毒GI. 1/G II. 4双价疫苗样颗粒（VLP）疫苗（含3-O-脱酰基-4 ′-单磷酰脂质A（MPL）和明矾）注射。参与者作为住院患者接受GII.4病毒（4400逆转录聚合酶链反应[RT-PCR]单位）的挑战，并监测疾病和感染。根据方案，50名疫苗接种者中有27名（54.0%）和48名对照者中有30名（62.5%）感染。使用预先定义的疾病和感染定义，疫苗接种不符合主要终点，但自我报告的严重（0%疫苗接种者vs 8.3%对照组; P = 0.054），中度或更高（6.0% vs 18.8%; P = 0.068），轻度或重度呕吐和/或腹泻（20.0% vs 37.5%; P = 0.074）发生率较低。疫苗接种也将改良Vesikari评分从7.3降至4.5（P = .002）。遇到的困难是诺如病毒病发病率低，无法通过定量RT-PCR确定疾病或由于疫苗诱导滴度高而导致接种者抗体进一步升高。到第10天，49名疫苗接种者中有11名（22.4%）脱落病毒，而47名安慰剂接种者中有17名（36.2%）脱落病毒（P = 0.179）。二价诺如病毒VLP疫苗减少了诺如病毒相关的呕吐和/或腹泻;计划进行田间有效性研究。NCT01609257。
Vaccines against norovirus, the leading cause of acute gastroenteritis, should protect against medically significant illness and reduce transmission. 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. 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). Bivalent norovirus VLP vaccine reduced norovirus-related vomiting and/or diarrhea; field efficacy studies are planned. NCT01609257.
登录
查看更多内容
DOI：
10.1056/nejmoa1101245
发表时间：
2011-12-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Atmar RL;Bernstein DI;Harro CD;Al-Ibrahim MS;Chen WH;Ferreira J;Estes MK;Graham DY;Opekun AR;Richardson C;Mendelman PM
通讯作者：
Mendelman PM
影响因子：
11.8
作者：
Scallan, Elaine;Griffin, Patricia M.;Hoekstra, Robert M.
通讯作者：
Hoekstra, Robert M.
影响因子：
5.4
作者：
Yang, Yang;Xia, Ming;Jiang, Xi
通讯作者：
Jiang, Xi
影响因子：
6.4
作者：
Treanor, John J.;Atmar, Robert L.;Mendelman, Paul M.
通讯作者：
Mendelman, Paul M.
诺如病毒和医学参加了美国儿童的胃肠炎。
DOI：
10.1056/nejmsa1206589
发表时间：
2013-03-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Payne DC;Vinjé J;Szilagyi PG;Edwards KM;Staat MA;Weinberg GA;Hall CB;Chappell J;Bernstein DI;Curns AT;Wikswo M;Shirley SH;Hall AJ;Lopman B;Parashar UD
通讯作者：
Parashar UD