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用编码牛呼吸道合胞病毒融合蛋白和核衣壳蛋白的质粒进行DNA免疫可诱导强烈的细胞介导免疫,并保护犊牛免受攻击。

DNA immunization with plasmids encoding fusion and nucleocapsid proteins of bovine respiratory syncytial virus induces a strong cell-mediated immunity and protects calves against challenge.

作者信息

Boxus Mathieu, Tignon Marylène, Roels Stefan, Toussaint Jean-François, Walravens Karl, Benoit Marie-Ange, Coppe Philippe, Letesson Jean-Jacques, Letellier Carine, Kerkhofs Pierre

机构信息

Biologie Cellulaire et Moléculaire, Faculté des Sciences Agronomiques, 5030 Gembloux, Belgium.

出版信息

J Virol. 2007 Jul;81(13):6879-89. doi: 10.1128/JVI.00502-07. Epub 2007 Apr 25.

Abstract

Respiratory syncytial viruses (RSV) are one of the most important respiratory pathogens of humans and cattle, and there is currently no safe and effective vaccine prophylaxis. In this study, we designed two codon-optimized plasmids encoding the bovine RSV fusion (F) and nucleocapsid (N) proteins and assessed their immunogenicity in young calves. Two administrations of both plasmids elicited low antibody levels but primed a strong cell-mediated immunity characterized by lymphoproliferative response and gamma interferon production in vitro and in vivo. Interestingly, this strong cellular response drastically reduced viral replication, clinical signs, and pulmonary lesions after a highly virulent challenge. Moreover, calves that were further vaccinated with a killed-virus vaccine developed high levels of neutralizing antibody and were fully protected following challenge. These results indicate that DNA vaccination could be a promising alternative to the classical vaccines against RSV in cattle and could therefore open perspectives for vaccinating young infants.

摘要

呼吸道合胞病毒(RSV)是人类和牛最重要的呼吸道病原体之一,目前尚无安全有效的疫苗预防措施。在本研究中,我们设计了两种密码子优化的质粒,分别编码牛RSV融合(F)蛋白和核衣壳(N)蛋白,并评估了它们在幼犊中的免疫原性。两种质粒各接种两次后诱导产生的抗体水平较低,但引发了强烈的细胞介导免疫,其特征为体外和体内的淋巴细胞增殖反应以及γ干扰素产生。有趣的是,这种强烈的细胞反应在高毒力攻击后大幅降低了病毒复制、临床症状和肺部病变。此外,用灭活病毒疫苗进一步接种的犊牛产生了高水平的中和抗体,并在攻击后得到了完全保护。这些结果表明,DNA疫苗可能是牛抗RSV经典疫苗的一种有前景的替代方法,因此可为婴幼儿接种疫苗开辟前景。

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