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猪CCL20趋化因子在针对猪瘟病毒DNA疫苗接种中的免疫调节作用。

Immunomodulatory effect of swine CCL20 chemokine in DNA vaccination against CSFV.

作者信息

Tarradas Joan, Álvarez Belen, Fraile Lorenzo, Rosell Rosa, Muñoz Marta, Galindo-Cardiel Iván, Domingo Mariano, Dominguez Javier, Ezquerra Angel, Sobrino Francisco, Ganges Llilianne

机构信息

Centre de Recerca en Sanitat Animal, IRTA-UAB, Campus de UAB, 08193 Bellaterra, Barcelona, Spain.

出版信息

Vet Immunol Immunopathol. 2011 Aug 15;142(3-4):243-51. doi: 10.1016/j.vetimm.2011.05.024. Epub 2011 May 26.

Abstract

The objective of this work was to explore whether a plasmid expressing CCL20 chemokine could improve the immune response against CSFV in co-administration with a DNA vaccine expressing the E2 protein. The immunization of pigs with the DNA vaccine formulation, that contains swine CCL20 chemokine, resulted in the homogenous induction of detectable levels of CSFV antibodies at 36 days after the first injection. Remarkably, immunized animals with E2 DNA vaccine in co-administration with the plasmid containing swine CCL20 developed high titers of neutralizing antibodies against homologous and heterologous CSFV strains and were totally protected upon a lethal viral challenge (sterilizing protection). Our results confirm the role of CCL20 to increase antibody-mediated responses. At the same time suggest the ability of CCL20 to enhance the T helper cell response associated with the induction of neutralizing antibodies against CSFV in pigs previously reported. Systemic replication of virulent CSFV in vivo during the acute phase of infection induces type I IFN. Lower average values of IFN alpha were detected in the serum of pigs immunized with pE2 and pCCL20 at 3 days after challenge. The levels of IFN-alpha detected in pigs immunized with pE2 and principally in non-vaccinated challenged animals can be related to viral load in serum at 3 and 7 days post infection and the clinical signs observed. Our results emphasized the capacity of swine CCL20 chemokine to enhance cellular, humoral and anti viral response with an adjuvant effect in the immune response elicited by E2-DNA vaccination against CSFV. To our knowledge, this is the first report demonstrating the adjuvant effect of swine CCL20 to effectively enhance the potential of DNA vaccine in the immune induction and protection against virus challenge in swine infection model.

摘要

本研究的目的是探索表达CCL20趋化因子的质粒与表达E2蛋白的DNA疫苗共同给药时,是否能增强针对猪瘟病毒(CSFV)的免疫反应。用含有猪CCL20趋化因子的DNA疫苗制剂免疫猪后,在首次注射后36天可均匀诱导出可检测水平的CSFV抗体。值得注意的是,用E2 DNA疫苗与含有猪CCL20的质粒共同免疫的动物产生了高滴度的针对同源和异源CSFV毒株的中和抗体,并在致死性病毒攻击后得到了完全保护(无菌保护)。我们的结果证实了CCL20在增强抗体介导反应中的作用。同时表明,CCL20有能力增强先前报道的与猪体内针对CSFV的中和抗体诱导相关的辅助性T细胞反应。在感染急性期,强毒CSFV在体内的系统性复制会诱导I型干扰素。在攻毒后3天,用pE2和pCCL20免疫的猪血清中检测到的干扰素α平均值较低。在用pE2免疫的猪以及主要在未接种疫苗的攻毒动物中检测到的干扰素α水平,可能与感染后3天和7天血清中的病毒载量以及观察到的临床症状有关。我们的结果强调了猪CCL20趋化因子在E2-DNA疫苗接种引发的针对CSFV的免疫反应中,具有增强细胞、体液和抗病毒反应以及辅助作用的能力。据我们所知,这是第一份证明猪CCL20在猪感染模型中具有辅助作用,能有效增强DNA疫苗免疫诱导潜力和抵抗病毒攻击能力的报告。

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