12月8日，《新英格兰医学杂志》上刊登了美国休斯顿Baylor医学院的RobertL.Atmar博士的一项概念性研究"Norovirus Vaccine against Experimental Human Norwalk Virus Illness"中，这项研究发现一种研究性诺如病毒疫苗对诺瓦克病毒感染及其相关性肠胃炎显示出保护作用。这种疫苗含有诺如病毒样微粒(VLP)和壳聚糖、单磷酰脂A佐剂，与安慰剂相比可使感染的相对风险降低26%，肠胃炎的相对风险降低47%。
RobertL.Atmar博士指出，这一发现表明“采用疫苗预防诺如病毒性疾病是有可能实现的”。诺如病毒感染目前在美国每年导致约2,100万例肠胃炎，仅在儿童中就导致约218,000例死亡。
这项双盲临床试验纳入了98名年龄18~50岁(平均32岁)的健康成年人，在4家临床医院对其进行随访。在试验的第一阶段，受试者被随组，接种研究性疫苗或安慰剂，鼻内给药2剂，之间间隔3周。在接种第2剂疫苗后3周时采集血清样本，以评估免疫原性。此时尚未退出研究的受试者进入第二阶段试验，在一家医院的住院部吞服诺瓦克病毒，留院观察肠胃炎发病情况并在必要时接受治疗。
共有89例受试者接受了2剂安慰剂或疫苗，84例受试者吞服了诺瓦克病毒。通过分析粪便样本，发现疫苗组和安慰剂组分别有61%和82%的受试者发生诺瓦克病毒感染，即接种疫苗使感染风险相对降低26%。疫苗组和安慰剂组分别有37%和69%的受试者发生诺瓦克病毒相关性肠胃炎，即风险相对降低47%。
不仅如此，疫苗炎组发生肠胃炎的受试者的病情严重程度显著低于安慰剂组，虽然总病程无显著差异，但疫苗组受试者发病时间延迟数小时。
总体而言，疫苗组70%的受试者显示出诺瓦克病毒特异性血清IgA抗体应答。“接种疫苗后产生血清抗体应答的几率和强度均低于感染引起的应答。自然感染后产生的免疫力较为‘短命’(仅能维持不足2年)，而因接种疫苗产生的免疫力的持续时间尚有待观察。”研究期间未发生疫苗相关性严重不良事件，也未出现预料之外的医疗状况。
研究者还对鼻内给药和肠外给药进行了比较，以确定最佳的常规给药途径。该研究中采用的鼻内给药系统数次发生故障，对疫苗给药产生了不利影响。
研究者认为，还需要进一步研究确定疫苗的免疫原性和对其他人群(尤其是儿童和老年人)的保护作用。“也许与轮状病毒疫苗相似，诺如病毒疫苗对重症患者可产生更强的保护作用。”
这项研究由上述疫苗的生产商LigoCyte制药和美国国立卫生研究院资助。Atmar博士报告称担任葛兰素史克、诺华和Haymarket传媒的顾问，他的合作者报告与诺华、Denka制药、全球疫苗、Immucell和EMMES公司有联系。（生物谷 Bioon.com）
doi:N. Engl. J. Med. 2011;365:2178-87
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PMID:
Norovirus Vaccine against Experimental Human Norwalk Virus Illness
Robert L. Atmar, M.D., David I. Bernstein, M.D., Clayton D. Harro, M.D., Mohamed S. Al-Ibrahim, M.B., Ch.B., Wilbur H. Chen, M.D., Jennifer Ferreira, Sc.M., Mary K. Estes, Ph.D., David Y. Graham, M.D., Antone R. Opekun, P.A.-C., Charles Richardson, Ph.D., and Paul M. Mendelman, M.D.
Background
Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection.
Methods
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.
Results
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 Norwalk 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).
Conclusions
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.)
