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首页> 外文期刊>Applied Microbiology and Biotechnology >Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
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Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences

机译：在小鼠中测试由嵌合Junin病毒样颗粒和保守的登革热病毒包膜序列制成的登革热疫苗候选物

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摘要

Two new vaccine candidates against dengue virus (DENV) infection were generated by fusing the coding sequences of the self-budding Z protein from Junin virus (Z-JUNV) to those of two cryptic peptides (Z/DENV-P1 and Z/DENV-P2) conserved on the envelope protein of all serotypes of DENV. The capacity of these chimeras to generate virus-like particles (VLPs) and to induce virus-neutralizing antibodies in mice was determined. First, recombinant proteins that displayed reactivity with a Z-JUNV-specific serum by immunofluorescence were detected in HEK-293 cells transfected with each of the two plasmids and VLP formation was also observed by transmission electron microscopy. Next, we determined the presence of antibodies against the envelope peptides of DENV in the sera of immunized C57BL/6 mice. Results showed that those animals that received Z/DENV-P2 DNA coding sequences followed by a boost with DENV-P2 synthetic peptides elicited significant specific antibody titers (>= 6.400). Finally, DENV plaque-reduction neutralization tests (PRNT) were performed. Although no significant protective effect was observed when using sera of Z/DENV-P1-immunized animals, antibodies raised against vaccine candidate Z/DENV-P2 (diluted 1:320) were able to reduce in over 50 % the number of viral plaques generated by infectious DENV particles. This reduction was comparable to that of the 4G2 DENV-specific monoclonal cross-reactive (all serotypes) neutralizing antibody. We conclude that Z-JUNV-VLP is a valid carrier to induce antibody-mediated immune responses in mice and that Z/DENV-P2 is not only immunogenic but also protective in vitro against infection of cells with DENV, deserving further studies. On the other side, DENV's fusion peptide-derived chimera Z/DENV-P1 did not display similar protective properties.
机译：通过将来自Junin病毒（Z-JUNV）的自芽Z蛋白的编码序列与两个隐性肽（Z / DENV-P1和Z / DENV- P2）在所有DENV血清型的包膜蛋白上均保守。确定了这些嵌合体在小鼠中产生病毒样颗粒（VLP）和诱导病毒中和抗体的能力。首先，在用两种质粒转染的HEK-293细胞中检测到通过免疫荧光显示与Z-JUNV特异性血清具有反应性的重组蛋白，并且还通过透射电子显微镜观察了VLP的形成。接下来，我们确定了在免疫的C57BL / 6小鼠血清中是否存在针对DENV包膜肽的抗体。结果表明，那些接受Z / DENV-P2 DNA编码序列并随后用DENV-P2合成肽加强免疫的动物引起了显着的特异性抗体效价（> = 6.400）。最后，进行了DENV斑块减少中和测试（PRNT）。尽管在使用经Z / DENV-P1免疫的动物的血清中未观察到明显的保护作用，但针对疫苗候选Z / DENV-P2的抗体（稀释比例为1：320）产生的病毒斑块数量减少了50％以上通过传染性的DENV颗粒。这种减少与4G2 DENV特异性单克隆交叉反应（所有血清型）中和抗体的减少相当。我们得出的结论是，Z-JUNV-VLP是诱导小鼠中抗体介导的免疫反应的有效载体，并且Z / DENV-P2不仅具有免疫原性，而且在体外对DENV细胞的感染具有保护作用，值得进一步研究。另一方面，DENV的融合肽衍生嵌合体Z / DENV-P1没有显示出相似的保护特性。

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