Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.

Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.
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人轮状病毒重组 VP8* 亚基肠外疫苗候选物的构建和表征。

DOI:
10.1016/j.vaccine.2012.07.078
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发表时间:
2012-09-21
期刊:
影响因子:
5.5
通讯作者:
Hoshino, Yasutaka
Hoshino, Yasutaka
中科院分区:
医学3区
文献类型:
--
作者:
Wen, Xiaobo;Cao, Dianjun;Jones, Ronald W.;Li, Jianping;Szu, Shousun;Hoshino, Yasutaka

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两种目前获得许可的口服轮状病毒活疫苗(Rotarix®和RotaTeq®)对严重的轮状病毒腹泻非常有效。然而,这类疫苗在某些低收入非洲和亚洲国家的效力远低于中等或高收入国家。此外,这两种疫苗最近与接种疫苗的婴儿中罕见的肠套叠病例有关。我们开发了一种新的重组亚单位肠胃外轮状病毒疫苗,可能在低收入国家更有效,也避免了潜在的肠套叠问题。人轮状病毒Wa P株[8]、DS-1 P株[4]和1076 P株[6]的截短重组VP 8 *(Δ VP 8 *)蛋白在E.大肠杆菌的可溶性高,产量高。用每种Δ VP 8 * 蛋白(即,(P[8],P[4]或P[6])产生高水平的同型中和抗体以及可变水平的异型中和抗体。此外,当以临床相关剂量、途径和时间表向小鼠施用所选Δ VP 8 * 蛋白时,引起高水平的血清抗VP 8 * IgG和/或中和抗体。我们的数据表明,Δ VP 8 * 蛋白可能是一个合理的额外的候选人作为新的肠胃外轮状病毒疫苗。
Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in E. coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., (P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines.
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