Lagerqvist Nina, Näslund Jonas, Lundkvist Ake, Bouloy Michèle, Ahlm Clas, Bucht Göran
Swedish Defence Research Agency, Department of CBRN Defence and Security, Umeå, Sweden.
Virol J. 2009 Jan 17;6:6. doi: 10.1186/1743-422X-6-6.
Affecting both livestock and humans, Rift Valley Fever is considered as one of the most important viral zoonoses in Africa. However, no licensed vaccines or effective treatments are yet available for human use. Naked DNA vaccines are an interesting approach since the virus is highly infectious and existing attenuated Rift Valley Fever virus vaccine strains display adverse effects in animal trials. In this study, gene-gun immunisations with cDNA encoding structural proteins of the Rift Valley Fever virus were evaluated in mice. The induced immune responses were analysed for the ability to protect mice against virus challenge.
Immunisation with cDNA encoding the nucleocapsid protein induced strong humoral and lymphocyte proliferative immune responses, and virus neutralising antibodies were acquired after vaccination with cDNA encoding the glycoproteins. Even though complete protection was not achieved by genetic immunisation, four out of eight, and five out of eight mice vaccinated with cDNA encoding the nucleocapsid protein or the glycoproteins, respectively, displayed no clinical signs of infection after challenge. In contrast, all fourteen control animals displayed clinical manifestations of Rift Valley Fever after challenge.
The appearance of Rift Valley Fever associated clinical signs were significantly decreased among the DNA vaccinated mice and further adjustment of this strategy may result in full protection against Rift Valley Fever.
裂谷热对牲畜和人类都有影响,被认为是非洲最重要的病毒性人畜共患病之一。然而,目前尚无获批用于人类的疫苗或有效治疗方法。由于该病毒具有高度传染性,且现有的减毒裂谷热病毒疫苗株在动物试验中显示出不良反应,裸DNA疫苗是一种值得关注的方法。在本研究中,对用编码裂谷热病毒结构蛋白的cDNA进行基因枪免疫的小鼠进行了评估。分析诱导的免疫反应保护小鼠免受病毒攻击的能力。
用编码核衣壳蛋白的cDNA免疫诱导了强烈的体液免疫和淋巴细胞增殖免疫反应,用编码糖蛋白的cDNA接种疫苗后获得了病毒中和抗体。尽管基因免疫未能实现完全保护,但分别用编码核衣壳蛋白或糖蛋白的cDNA接种疫苗的八只小鼠中有四只和八只小鼠中有五只在攻击后未表现出感染的临床症状。相比之下,所有十四只对照动物在攻击后均表现出裂谷热的临床表现。
DNA疫苗接种小鼠中与裂谷热相关的临床症状出现率显著降低,进一步调整该策略可能会实现对裂谷热的完全保护。