Norovirus vaccine against experimental human Norwalk Virus illness.
Norovirus vaccine against experimental human Norwalk Virus illness.
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DOI：
10.1056/nejmoa1101245
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发表时间：
2011-12-08
期刊：
影响因子：
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通讯作者：
Mendelman PM
中科院分区：
文献类型：
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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
诺如病毒引起流行性和散发性急性胃肠炎。没有疫苗可用于预防诺如病毒疾病或感染。我们进行了一项随机、双盲、安慰剂对照、多中心试验，以评估一种研究性鼻内给药诺如病毒病毒样颗粒（VLP）疫苗（以壳聚糖和单磷酰脂质A作为佐剂）预防同源病毒株诺瓦克病毒（基因型GI. 1）攻击后急性病毒性胃肠炎的安全性、免疫原性和有效性。18至50岁的健康成年人接受两剂疫苗或安慰剂，随后接种诺瓦克病毒，并监测感染和胃肠炎症状。98人被招募并随机分配接受疫苗（50名参与者）或安慰剂（48名参与者），90人接受两种剂量（疫苗组47名参与者和安慰剂组43名参与者）。接种疫苗后最常报告的症状是鼻塞、流涕和打喷嚏。疫苗接种者和安慰剂接种者的不良事件发生频率相似。在70%的疫苗接种者中检测到诺瓦克病毒特异性伊加血清应答（定义为血清抗体水平增加4倍）。84名接种诺瓦克病毒的参与者中有77名被纳入符合方案分析。接种疫苗显著降低了诺瓦克病毒胃肠炎（安慰剂组69%，疫苗组37%，P = 0.006）和诺瓦克病毒感染（安慰剂组82%，疫苗组61%，P = 0.05）的发生率。这种诺如病毒VLP疫苗在用同源病毒攻击后提供针对疾病和感染的保护。（由LigoCyte Pharmaceuticals和美国国立卫生研究院资助; ClinicalTrials.gov编号，NCT 00973284。
Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection. We conducted a randomized, double-blind, placebo-controlled, multicenter trial to assess the safety, immunogenicity, and efficacy of an investigational, intranasally delivered norovirus viruslike particle (VLP) vaccine (with chitosan and monophosphoryl lipid A as adjuvants) to prevent acute viral gastroenteritis after challenge with a homologous viral strain, Norwalk virus (genotype GI.1). Healthy adults 18 to 50 years of age received two doses of either vaccine or placebo and were subsequently inoculated with Norwalk virus and monitored for infection and gastroenteritis symptoms. Ninety-eight persons were enrolled and randomly assigned to receive vaccine (50 participants) or placebo (48 participants), and 90 received both doses (47 participants in the vaccine group and 43 in the placebo group). The most commonly reported symptoms after vaccination were nasal stuffiness, nasal discharge, and sneezing. Adverse events occurred with similar frequency among vaccine and placebo recipients. A Nor-walk virus–specific IgA seroresponse (defined as an increase by a factor of 4 in serum antibody levels) was detected in 70% of vaccine recipients. Seventy-seven of 84 participants inoculated with Norwalk virus were included in the per-protocol analysis. Vaccination significantly reduced the frequencies of Norwalk virus gastroenteritis (occurring in 69% of placebo recipients vs. 37% of vaccine recipients, P = 0.006) and Norwalk virus infection (82% of placebo recipients vs. 61% of vaccine recipients, P = 0.05). This norovirus VLP vaccine provides protection against illness and infection after challenge with a homologous virus. (Funded by LigoCyte Pharmaceuticals and the National Institutes of Health; ClinicalTrials.gov number, NCT00973284.)