12月8日，《新英格蘭醫(yī)學雜志》上刊登了美國休斯頓Baylor醫(yī)學院的RobertL.Atmar博士的一項概念性研究"Norovirus Vaccine against Experimental Human Norwalk Virus Illness"中,，這項研究發(fā)現(xiàn)一種研究性諾如病毒疫苗對諾瓦克病毒感染及其相關性腸胃炎顯示出保護作用,。這種疫苗含有諾如病毒樣微粒(VLP)和殼聚糖、單磷酰脂A佐劑,，與安慰劑相比可使感染的相對風險降低26%,，腸胃炎的相對風險降低47%。
RobertL.Atmar博士指出,，這一發(fā)現(xiàn)表明“采用疫苗預防諾如病毒性疾病是有可能實現(xiàn)的”,。諾如病毒感染目前在美國每年導致約2,100萬例腸胃炎，僅在兒童中就導致約218,000例死亡,。
這項雙盲臨床試驗納入了98名年齡18~50歲(平均32歲)的健康成年人,，在4家臨床醫(yī)院對其進行隨訪。在試驗的第一階段,，受試者被隨組,，接種研究性疫苗或安慰劑，鼻內給藥2劑,，之間間隔3周,。在接種第2劑疫苗后3周時采集血清樣本，以評估免疫原性,。此時尚未退出研究的受試者進入第二階段試驗,，在一家醫(yī)院的住院部吞服諾瓦克病毒,，留院觀察腸胃炎發(fā)病情況并在必要時接受治療。
共有89例受試者接受了2劑安慰劑或疫苗,，84例受試者吞服了諾瓦克病毒,。通過分析糞便樣本，發(fā)現(xiàn)疫苗組和安慰劑組分別有61%和82%的受試者發(fā)生諾瓦克病毒感染,，即接種疫苗使感染風險相對降低26%,。疫苗組和安慰劑組分別有37%和69%的受試者發(fā)生諾瓦克病毒相關性腸胃炎，即風險相對降低47%,。
不僅如此,，疫苗炎組發(fā)生腸胃炎的受試者的病情嚴重程度顯著低于安慰劑組，雖然總病程無顯著差異,，但疫苗組受試者發(fā)病時間延遲數(shù)小時,。
總體而言，疫苗組70%的受試者顯示出諾瓦克病毒特異性血清IgA抗體應答,。“接種疫苗后產(chǎn)生血清抗體應答的幾率和強度均低于感染引起的應答,。自然感染后產(chǎn)生的免疫力較為‘短命’(僅能維持不足2年)，而因接種疫苗產(chǎn)生的免疫力的持續(xù)時間尚有待觀察,。”研究期間未發(fā)生疫苗相關性嚴重不良事件,，也未出現(xiàn)預料之外的醫(yī)療狀況。
研究者還對鼻內給藥和腸外給藥進行了比較,，以確定最佳的常規(guī)給藥途徑,。該研究中采用的鼻內給藥系統(tǒng)數(shù)次發(fā)生故障，對疫苗給藥產(chǎn)生了不利影響,。
研究者認為,，還需要進一步研究確定疫苗的免疫原性和對其他人群(尤其是兒童和老年人)的保護作用。“也許與輪狀病毒疫苗相似,，諾如病毒疫苗對重癥患者可產(chǎn)生更強的保護作用,。”
這項研究由上述疫苗的生產(chǎn)商LigoCyte制藥和美國國立衛(wèi)生研究院資助。Atmar博士報告稱擔任葛蘭素史克,、諾華和Haymarket傳媒的顧問,，他的合作者報告與諾華、Denka制藥,、全球疫苗,、Immucell和EMMES公司有聯(lián)系。（生物谷 Bioon.com）
doi:N. Engl. J. Med. 2011;365:2178-87
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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.)
