Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans.
Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans.
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DOI：
10.1093/cid/cis327
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Gilbert SC
中科院分区：
文献类型：
--
作者：
Lillie PJ;Berthoud TK;Powell TJ;Lambe T;Mullarkey C;Spencer AJ;Hamill M;Peng Y;Blais ME;Duncan CJ;Sheehy SH;Havelock T;Faust SN;Williams RL;Gilbert A;Oxford J;Dong T;Hill AV;Gilbert SC
MVA-NP+M1单次疫苗接种可增强人类对保守流感抗原的T细胞应答。在流感病毒攻毒研究中证明了对流感疾病和病毒脱落的保护作用。背景：新型流感疫苗MVA-NP+M1被设计为增强对所有亚型中保守的甲型流感病毒内部抗原的交叉反应性T细胞应答，提供针对流感疾病和针对所有甲型流感病毒的病毒脱落的保护。 在证明疫苗安全性和免疫原性的I期临床研究之后，在健康成人志愿者中进行了IIa期疫苗接种和流感攻毒研究。方法：没有可测量的A/威斯康星州/67/2005流感血清抗体的志愿者接受MVA-NP+M1单次疫苗接种或不接种。 在入组时和病毒攻击前再次测量对疫苗抗原的T细胞应答。所有志愿者在隔离病房接受流感A/威斯康星州/67/2005鼻内给药，并监测流感疾病症状和病毒脱落。结果：志愿者在单次接种疫苗后，对疫苗抗原的T细胞应答显著增加，溶细胞效应分子增加。 进行鼻内流感攻毒，未出现安全性问题。11名接种者中的2名和11名对照受试者中的5名发生实验室确认的流感（症状加病毒脱落）。接种者的流感症状不太明显，发生流感的接种者的病毒脱落天数显著减少（对照组平均为1.09天，接种者为0.45天，P = 0.036）。结论：本研究首次证明了基于T细胞的流感疫苗的临床有效性，并指出应进行进一步的临床开发。 临床试验注册NCT 00993083。
A single vaccination with MVA-NP+M1 boosts T-cell responses to conserved influenza antigens in humans. Protection against influenza disease and virus shedding was demonstrated in an influenza virus challenge study. Background. The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers. Methods. Volunteers with no measurable serum antibodies to influenza A/Wisconsin/67/2005 received either a single vaccination with MVA-NP+M1 or no vaccination. T-cell responses to the vaccine antigens were measured at enrollment and again prior to virus challenge. All volunteers underwent intranasal administration of influenza A/Wisconsin/67/2005 while in a quarantine unit and were monitored for symptoms of influenza disease and virus shedding. Results. Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules. Intranasal influenza challenge was undertaken without safety issues. Two of 11 vaccinees and 5 of 11 control subjects developed laboratory-confirmed influenza (symptoms plus virus shedding). Symptoms of influenza were less pronounced in the vaccinees and there was a significant reduction in the number of days of virus shedding in those vaccinees who developed influenza (mean, 1.09 days in controls, 0.45 days in vaccinees, P = .036). Conclusions. This study provides the first demonstration of clinical efficacy of a T-cell–based influenza vaccine and indicates that further clinical development should be undertaken. Clinical Trials Registration. NCT00993083.
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通过合成共识DNA抗原的体内电穿孔对致病性人类和鸟类流感病毒的杂型保护。
影响因子：
3.7
作者：
Laddy, Dominick J.;Yan, Jian;Kutzler, Michele;Kobasa, Darwyn;Kobinger, Gary P.;Khan, Amir S.;Greenhouse, Jack;Sardesai, Niranjan Y.;Draghia-Akli, Ruxandra;Weiner, David B.
通讯作者：
Weiner, David B.
影响因子：
5.4
作者：
Laddy, Dominick J.;Yan, Jian;Weiner, David B.
通讯作者：
Weiner, David B.
DOI：
10.1093/cid/ciq015
发表时间：
2011-01-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Berthoud TK;Hamill M;Lillie PJ;Hwenda L;Collins KA;Ewer KJ;Milicic A;Poyntz HC;Lambe T;Fletcher HA;Hill AV;Gilbert SC
通讯作者：
Gilbert SC
影响因子：
82.9
作者：
DONNELLY, JJ;FRIEDMAN, A;LIU, MA
通讯作者：
LIU, MA
影响因子：
6.4
作者：
Epstein, SL
通讯作者：
Epstein, SL