Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV.
Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV.
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DOI：
10.1371/journal.pone.0081472
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ackermann MR
中科院分区：
文献类型：
--
作者：
Derscheid RJ;Gallup JM;Knudson CJ;Varga SM;Grosz DD;van Geelen A;Hostetter SJ;Ackermann MR
呼吸道合胞病毒(RSV)是全世界婴儿和儿童毛细支气管炎的最常见原因。目前还没有获得许可的疫苗或有效的抗病毒药物。缺乏疫苗的部分原因是在20世纪60年代进行的福尔马林灭活呼吸道合胞病毒疫苗(FI-RSV)临床试验失败后，人们更加谨慎，导致疾病加剧，80%的疫苗接受者需要住院治疗，并导致两人死亡。围产期的羔羊肺在大小、结构和生理上与人类婴儿的相似，并且容易受到人类RSV毒株的影响，这种病毒会引起与受感染的人类婴儿相似的损害。我们试图确定用FI-RSV免疫的围产期羔羊是否会产生疫苗增强型疾病的关键特征。这在剥夺初乳的羔羊身上进行了测试，这些羔羊在3-5天龄时接种了FI-RSV，两周后感染了RSV。接种FI-RSV疫苗的羔羊表现出RSV疫苗增强型疾病的几个关键特征，包括肺泡灌洗液和肺中RSV滴度降低，与急性RSV感染或幼稚对照羔羊相比，细支气管周和血管周围淋巴细胞的渗透增加；所有这些特征都是RSV疫苗增强型疾病的特征。这些结果代表了第一步的原则证明，即羔羊在接种FI-RSV疫苗后可以对RSV产生改变的反应。羔羊模型可能对未来的机理研究以及为婴儿设计的RSV疫苗的评估有用。
Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960’s that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3–5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.
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影响因子：
2.3
作者：
Lazic, Tatjana;Wyatt, Todd A.;Ackermann, Mark R.
通讯作者：
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DOI：
10.1126/science.1234914
发表时间：
2013-05-31
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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DOI：
10.1111/j.1365-2613.2009.00643.x
发表时间：
2009-08
影响因子：
3
作者：
Olivier A;Gallup J;de Macedo MM;Varga SM;Ackermann M
通讯作者：
Ackermann M
影响因子：
1.7
作者：
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通讯作者：
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