State Key Laboratory for Molecular Virology and Genetic Engineering, Institute for Viral Disease Control and Prevention, China CDC, 155 Chang Bai Road, Chang Ping District, Beijing 102206, China.
Virol J. 2011 Jun 30;8:333. doi: 10.1186/1743-422X-8-333.
The incidence of dengue, an infectious disease caused by dengue virus (DENV), has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs) has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated.
By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses.
Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.
登革热是由登革病毒(DENV)引起的传染病,近几十年来在全球范围内发病率急剧上升,成为严重的公共卫生威胁。然而,目前尚无针对登革热的特定治疗方法,也没有获得许可的登革热疫苗。病毒样颗粒(VLPs)疫苗已在许多病毒性疾病中显示出相当大的前景,但 DENV VLPs 诱导特异性免疫反应的效果尚未得到充分研究。
通过优化表达质粒,在 293T 细胞中成功表达了四种抗原不同的 DENV 血清型 DENV1-4 的重组 VLPs。登革热 VLPs 在小鼠中的免疫效果表明,每种血清型的单价 VLPs 均能刺激针对同源病毒的特异性 IgG 反应和强效中和抗体。四价 VLPs 能有效增强针对 DENV 四种血清型的特异性 IgG 和中和抗体。此外,单价或四价 VLPs 疫苗接种可诱导特异性细胞毒性 T 细胞反应。
哺乳动物细胞表达的登革热 VLPs 能够在小鼠中诱导 VLP 特异性体液和细胞免疫反应,是预防登革病毒感染的有前途的亚单位候选疫苗。