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Baculovirus vectors expressing F proteins in combination with virus-induced signaling adaptor (VISA) molecules confer protection against respiratory syncytial virus infection.
Vaccine ( IF 5.5 ) Pub Date : 2015-12-09 , DOI: 10.1016/j.vaccine.2015.11.027
Yuan Zhang 1 , Lei Qiao 1 , Xiao Hu 1 , Kang Zhao 1 , Yanwen Zhang 1 , Feng Chai 1 , Zishu Pan 1
Affiliation  

Baculovirus has been exploited for use as a novel vaccine vector. To investigate the feasibility and efficacy of recombinant baculoviruses (rBVs) expressing respiratory syncytial virus (RSV) fusion (F) proteins, four constructs (Bac-tF/64, Bac-CF, Bac-CF/tF64 and Bac-CF/tF64-VISA) were generated. Bac-tF64 displays the F ectodomain (tF) on the envelope of rBVs, whereas Bac-CF expresses full-length F protein in transduced mammalian cells. Bac-CF/tF64 not only displays tF on the envelope but also expresses F in cells. Bac-CF/tF64-VISA comprises Bac-CF/tF64 harboring the virus-induced signaling adaptor (VISA) gene. After administration to BALB/c mice, all four vectors elicited RSV neutralizing antibody (Ab), systemic Ab (IgG, IgG1, and IgG2a), and cytokine responses. Compared with Bac-tF64, mice inoculated with Bac-CF and Bac-CF/tF64 exhibited an increased mixed Th1/Th2 cytokine response, increased ratios of IgG2a/IgG1 antibody responses, and reduced immunopathology upon RSV challenge. Intriguingly, co-expression of VISA reduced Th2 cytokine (IL-4, IL-5, and IL-10) production induced by Bac-CF/tF64, thus relieving lung pathology upon a subsequent RSV challenge. Our results indicated that the Bac-CF/tF64 vector incorporated with the VISA molecule may provide an effective vaccine strategy for protection against RSV.

中文翻译:

表达F蛋白的杆状病毒载体与病毒诱导的信号衔接子(VISA)分子结合,可预防呼吸道合胞病毒感染。

杆状病毒已被开发用作新型疫苗载体。为了研究表达呼吸道合胞病毒(RSV)融合(F)蛋白的重组杆状病毒(rBV)的可行性和功效,使用了四种构建体(Bac-tF / 64,Bac-CF,Bac-CF / tF64和Bac-CF / tF64- VISA)。Bac-tF64在rBV的外壳上显示F胞外域(tF),而Bac-CF在转导的哺乳动物细胞中表达全长F蛋白。Bac-CF / tF64不仅在信封上显示tF,而且还在细胞中表达F。Bac-CF / tF64-VISA包含Bac-CF / tF64,带有病毒诱导的信号转接头(VISA)基因。给BALB / c小鼠给药后,所有四个载体均引发RSV中和抗体(Ab),全身性Ab(IgG,IgG1和IgG2a)和细胞因子应答。与Bac-tF64相比,接种Bac-CF和Bac-CF / tF64的小鼠表现出增加的Th1 / Th2细胞因子混合应答,IgG2a / IgG1抗体应答比率增加以及RSV攻击后免疫病理降低。有趣的是,VISA的共表达减少了由Bac-CF / tF64诱导的Th2细胞因子(IL-4,IL-5和IL-10)的产生,从而减轻了随后RSV攻击后的肺部病变。我们的结果表明,与VISA分子结合的Bac-CF / tF64载体可为保护RSV提供有效的疫苗策略。
更新日期:2015-11-28
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