PDF(Pubmed)
Abstract：
BACKGROUND: A vaccine against Trypanosoma cruzi, the agent of Chagas disease, would be an excellent additional tool for disease control. A recombinant vaccine based on Tc24 and TSA1 parasite antigens was found to be safe and immunogenic in naïve macaques.
METHODS: We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the optimization of doses and formulation. We identified differentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires.
RESULTS: RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profile. Analysis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose.
CONCLUSIONS: These data suggest that three vaccine doses may be needed for optimum immunogenicity and support the further evaluation of the protective efficacy of this vaccine.
METHODS: We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the optimization of doses and formulation. We identified differentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires.
RESULTS: RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profile. Analysis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose.
CONCLUSIONS: These data suggest that three vaccine doses may be needed for optimum immunogenicity and support the further evaluation of the protective efficacy of this vaccine.
摘要：
背景：一种针对克氏锥虫的疫苗，查加斯病的代理人，将是疾病控制的一个极好的额外工具。发现基于Tc24和TSA1寄生虫抗原的重组疫苗在初始猕猴中是安全且具有免疫原性的。
方法：我们使用RNA测序，并在每次疫苗剂量后对未接种猕猴的PBMC反应进行转录组学分析，阐明该疫苗的免疫原性，并指导剂量和配方的优化。我们鉴定了差异表达的基因和途径，并表征了免疫球蛋白和T细胞受体库。
结果：RNA测序分析表明，三剂疫苗后，PBMC的转录组反应明显，随着几种免疫细胞活化途径的上调和广泛的非极化免疫谱。对IgG库的分析表明，它具有快速的更新，每次疫苗剂量后产生的新型IgG，而TCR库呈现了几个持续的克隆，这些克隆在每次疫苗剂量后扩增。
结论：这些数据表明，为了获得最佳的免疫原性，可能需要三种疫苗剂量，并支持进一步评估该疫苗的保护效力。
方法：我们使用RNA测序，并在每次疫苗剂量后对未接种猕猴的PBMC反应进行转录组学分析，阐明该疫苗的免疫原性，并指导剂量和配方的优化。我们鉴定了差异表达的基因和途径，并表征了免疫球蛋白和T细胞受体库。
结果：RNA测序分析表明，三剂疫苗后，PBMC的转录组反应明显，随着几种免疫细胞活化途径的上调和广泛的非极化免疫谱。对IgG库的分析表明，它具有快速的更新，每次疫苗剂量后产生的新型IgG，而TCR库呈现了几个持续的克隆，这些克隆在每次疫苗剂量后扩增。
结论：这些数据表明，为了获得最佳的免疫原性，可能需要三种疫苗剂量，并支持进一步评估该疫苗的保护效力。
