The rational simplification of a recombinant cocktail vaccine to control the parasitic nematode Teladorsagia circumcincta
The rational simplification of a recombinant cocktail vaccine to control the parasitic nematode Teladorsagia circumcincta
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DOI：
10.1016/j.ijpara.2018.10.006
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Matthews, Jacqueline B.
中科院分区：
文献类型：
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作者：
Nisbet, Alasdair J.;McNeilly, Tom N.;Matthews, Jacqueline B.
利用五项独立疫苗试验的数据，研究人员开发了一种简化疫苗抗原复杂性的策略，这些试验采用了一种含有8种重组蛋白的亚基鸡尾酒疫苗来保护绵羊免受割礼靶藻的侵害。对这五项试验数据的荟萃分析显示，与仅接种佐剂的绵羊相比，接种疫苗的绵羊的累积粪卵计数和蠕虫负荷显著减少（P = 0.009和P < 0.0001）。在这些试验中，分析了抗原特异性抗体水平、抗体贪婪度和功效的寄生虫学参数之间的关系。其中，与血清中总抗原特异性IgG或IgG1相关的疫苗抗原环切T. apyase -1 （Tci-APY-1）的累积粪卵数减少百分比与贪婪度之间的相关性最强（P = 0.019和P = 0.030分别）。此外，对照羔羊血清和胃黏膜粘液中的lgG和IgA能强烈识别Tci-APY-1和T.环切金属蛋白酶-1 (Tci-MEP-1)，而与其他6种抗原结合较弱，表明Tci-APY-1和Tci-MEP-1在寄生虫诱导的抗体应答中最有效识别。在这些发现的基础上，对含有Tci-APY-1和Tci-MEP-1的双蛋白疫苗进行了测试，并与最初的八组分疫苗进行了直接比较。另一组用Tci-MEP-1与突变形式的Tci-APY-1 （mTci-APY-1）联合免疫，该突变形式没有酶活性。在整个试验中，8种抗原受体的平均粪卵计数水平低于单纯佐剂对照组（P = 0.013）， mTci-APY-1和Tci-MEP-1受体的平均FEC低于单纯佐剂对照组（P = 0.093），但无统计学意义。与对照组相比，接种mTci-APY-1 + Tci-MEP-1的羔羊平均累积粪蛋数水平降低了43% （P = 0.079）。(C) 2019作者。由Elsevier Ltd代表澳大利亚寄生虫学学会出版。这是一篇基于CC BY-NC-ND许可（http://creativecommons.orgilicensesiby-nc-nd/4.0/）的开放获取文章。
Using data from five independent vaccine trials, which employed a subunit cocktail vaccine containing eight recombinant proteins to protect sheep against Teladorsagia circumcincta, a strategy was developed to simplify antigen complexity of the vaccine. A meta-analysis of data from these five trials demonstrated statistically significant reductions in cumulative faecal egg count and worm burden in vaccinated sheep when compared with those which had received adjuvant only (P = 0.009 and P < 0.0001, respectively). Relationships between antigen-specific antibody levels, antibody avidity and parasitological parameters of efficacy were analysed for each of the eight proteins in these trials. Of these, the strongest correlations between percentage reduction in cumulative faecal egg count and avidity were obtained for the vaccine antigen T. circumcincta apyrase-1 (Tci-APY-1) in relation to either total antigen-specific IgG or IgG1 in sera (P = 0.019 and P = 0.030, respectively). In addition, lgG and IgA within the serum and abomasal mucus of control (parasite challenged) lambs strongly recognised Tci-APY-1 and T. circumcincta metalloproteinase-1 (Tci-MEP-1) but only weakly bound the other six antigens, indicating Tci-APY-1 and Tci-MEP-1 are most effectively recognised by the parasite-induced antibody response. On the basis of these findings, a two-protein vaccine comprising Tci-APY-1 and Tci-MEP-1 was tested in a direct comparison with the original eight-component vaccine. A further group was immunised with Tci-MEP-1 in combination with a mutated form of Tci-APY-1 (mTci-APY-1), which had no enzymatic activity. Across the trial, the mean faecal egg count levels of the eight-antigen recipients were lower than those of the adjuvant only control group (P = 0.013) and the mean FEC of the mTci-APY-1 and Tci-MEP-1 recipients was lower, although not statistically significantly, than that of the adjuvant-only control group (P = 0.093). Mean cumulative faecal egg count levels were reduced by 43% in lambs immunised with mTci-APY-1 plus Tci-MEP-1 compared with the controls (P = 0.079). (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.orgilicensesiby-nc-nd/4.0/).