A single vaccination with an improved nonspreading Rift Valley fever virus vaccine provides sterile immunity in lambs.
A single vaccination with an improved nonspreading Rift Valley fever virus vaccine provides sterile immunity in lambs.
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DOI：
10.1371/journal.pone.0077461
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kortekaas J
中科院分区：
文献类型：
--
作者：
Oreshkova N;van Keulen L;Kant J;Moormann RJ;Kortekaas J
裂谷热病毒(RVFV)是影响反刍动物和人类的重要病原体。最近，我们开发了一种基于非传播性RVFV(NSR)的疫苗，并表明该疫苗一次接种可以保护羔羊免受病毒血症和临床症状的影响。然而，在攻击感染后不久，接种疫苗的羔羊血液中检测到低水平的病毒RNA。当怀孕母羊体内存在这些低水平的病毒时，可能会感染高度敏感的胎儿。因此，我们的目标是进一步提高NSR疫苗的效力。在这里，我们报告了病毒的主要免疫原蛋白Gn在NSR基因组中的表达。由此产生的NSR-Gn疫苗被证明在小鼠中激发了更好的CD8和CD4限制性记忆反应，并提高了病毒中和效价。对羔羊的剂量滴定研究表明，最高接种剂量为106.3 TCID50/ml，可保护所有羔羊免受临床症状和病毒血症的影响。这些羔羊在免疫后三周内产生中和抗体，在攻击后没有观察到记忆反应。综合结果表明，一次接种NSR-Gn疫苗即可获得无菌免疫。
Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 106.3 TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine.
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DOI：
10.20506/rst.27.2.1817
发表时间：
2008-08-01
影响因子：
0.6
作者：
Dufour, B.;Moutou, F.;Rodhain, F.
通讯作者：
Rodhain, F.
影响因子：
3.7
作者：
Gorchakov, Rodion;Volkova, Eugenia;Frolov, Ilya
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影响因子：
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作者：
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影响因子：
5.5
作者：
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Bouloy, Michele
影响因子：
5.5
作者：
de Boer, S. M.;Kortekaas, J.;Bosch, B. J.
通讯作者：
Bosch, B. J.