Bivalent rotavirus VP4∗ stimulates protective antibodies against common genotypes of human rotaviruses.

Bivalent rotavirus VP4∗ stimulates protective antibodies against common genotypes of human rotaviruses.
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DOI:
10.1016/j.isci.2022.105099
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发表时间:
2022-10-21
期刊:
影响因子:
5.8
通讯作者:
Xia, Ningshao
Xia, Ningshao
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Luo, Guoxing;Zeng, Yuanjun;Yang, Han;Li, Yijian;Yang, Lianwei;Li, Cao;Song, Feibo;Zhang, Shiyin;Li, Tingdong;Ge, Shengxiang;Zhang, Jun;Xia, Ningshao

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非复制型轮状病毒疫苗是提高轮状病毒疫苗功效和安全性的替代策略。刺突蛋白 VP4 可被酶切为 VP8* 和 VP5*,是开发重组轮状病毒疫苗的理想靶标。在我们之前的研究中,我们证明了与 VP8* 和 VP5* 相比,截短的 VP4(aa26-476,VP4*)可能是更可行的候选疫苗。为了开发人轮状病毒疫苗,表达了 P[4]、P[6] 和 P[8] 基因型轮状病毒的 VP4* 蛋白。当配制在铝佐剂中时,所有 VP4* 蛋白都能刺激豚鼠和兔子产生高水平的中和抗体。此外,基于二价 VP4* 的疫苗 (P[8] + P[6]-VP4*) 可以刺激高水平的针对各种轮状病毒基因型的中和抗体,与三价疫苗相比没有显着差异。因此,二价 VP4* 有潜力成为进一步开发的可行的轮状病毒疫苗候选者。纯化的轮状病毒 VP4* 蛋白形成同源且稳定的三聚体 VP4* 刺激高水平的同型和异型中和抗体 不同基因型 VP4* 的免疫原性不受彼此影响 二价 VP4* (P[8]+P[6]) 刺激针对最流行的轮状病毒的保护性免疫 生物科学;微生物学;病毒学;病毒微生物学
Non-replicating rotavirus vaccines are an alternative strategy to improve the efficacy and safety of rotavirus vaccines. The spike protein VP4, which could be enzymatically cleaved into VP8∗ and VP5∗, is an ideal target for the development of recombinant rotavirus vaccine. In our previous studies, we demonstrated that the truncated VP4 (aa26-476, VP4∗) could be a more viable vaccine candidate compared to VP8∗ and VP5∗. Here, to develop a human rotavirus vaccine, the VP4∗ proteins of P[4], P[6], and P[8] genotype rotaviruses were expressed. All VP4∗ proteins can stimulate high levels of neutralizing antibodies in both guinea pigs and rabbits when formulated in aluminum adjuvant. Furthermore, bivalent VP4∗-based vaccine (P[8] + P[6]-VP4∗) can stimulate high levels of neutralizing antibodies against various genotypes of rotavirus with no significant difference as compared to the trivalent vaccines. Therefore, bivalent VP4∗ has the potential to be a viable rotavirus vaccine candidate for further development. Purified rotavirus VP4∗ proteins form homogenic and stable trimers VP4∗ stimulated high levels of homotypic and heterotypic neutralizing antibodies The immunogenicity of different genotype VP4∗ is not influenced by each other Bivalent VP4∗ (P[8]+P[6]) stimulated protective immunity against most prevalent rotaviruses Biological sciences; Microbiology; Virology; Viral microbiology
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