Moredun Research Institute, Pentlands Science Park, Edinburgh EH26 0PZ, United Kingdom.
Moredun Research Institute, Pentlands Science Park, Edinburgh EH26 0PZ, United Kingdom.
Int J Parasitol. 2019 Mar;49(3-4):257-265. doi: 10.1016/j.ijpara.2018.10.006. Epub 2019 Jan 26.
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, IgG 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).
使用包含八种重组蛋白的亚单位鸡尾酒疫苗来保护绵羊免受细颈线虫感染的五项独立疫苗试验的数据，开发了一种简化疫苗抗原复杂性的策略。对这五项试验的数据进行的荟萃分析表明，与仅接受佐剂的绵羊相比，接种疫苗的绵羊的累积粪便卵计数和蠕虫负担有统计学意义的降低（分别为 P=0.009 和 P<0.0001）。分析了这些试验中每一种八种蛋白的抗原特异性抗体水平、抗体亲和力与寄生虫学疗效参数之间的关系。在这些相关性中，与累积粪便卵计数的百分比降低之间相关性最强的是疫苗抗原 T. circumcincta 脱氨酶-1（Tci-APY-1），无论是与血清中的总抗原特异性 IgG 还是 IgG1 相关（分别为 P=0.019 和 P=0.030）。此外，在对照（寄生虫挑战）羔羊的血清和皱胃粘液中，IgG 和 IgA 强烈识别 Tci-APY-1 和 T. circumcincta 金属蛋白酶-1（Tci-MEP-1），但仅弱结合其他六种抗原，表明 Tci-APY-1 和 Tci-MEP-1 是最有效地被寄生虫诱导的抗体反应所识别。基于这些发现，一种由 Tci-APY-1 和 Tci-MEP-1 两种蛋白组成的疫苗在与原始的八种成分疫苗的直接比较中进行了测试。还有一组用 Tci-MEP-1 与一种无酶活性的突变 Tci-APY-1（mTci-APY-1）组合进行免疫。在整个试验中，接受八种抗原的羔羊的平均粪便卵计数水平低于仅接受佐剂的对照组（P=0.013），而接受 mTci-APY-1 和 Tci-MEP-1 的羔羊的平均 FEC 虽然低于但无统计学意义低于仅接受佐剂的对照组（P=0.093）。与对照组相比，用 mTci-APY-1 加 Tci-MEP-1 免疫的羔羊的累积粪便卵计数水平降低了 43%（P=0.079）。
