Grund Megan E, Kramarska Eliza, Choi Soo Jeon, McNitt Dudley H, Klimko Christopher P, Rill Nathaniel O, Dankmeyer Jennifer L, Shoe Jennifer L, Hunter Melissa, Fetterer David P, Hedrick Zander M, Velez Ivan, Biryukov Sergei S, Cote Christopher K, Berisio Rita, Lukomski Slawomir
Department of Microbiology, Immunology and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
Institute of Biostructures and Bioimaging, National Research Council (CNR-IBB), 80134 Naples, Italy.
Vaccines (Basel). 2021 Oct 20;9(11):1219. doi: 10.3390/vaccines9111219.
is an infectious bacterium of clinical and biodefense concern, and is the causative agent of melioidosis. The mortality rate can reach up to 50% and affects 165,000 people per year; however, there is currently no vaccine available. In this study, we examine the antigen-specific immune response to a vaccine formulated with antigens derived from an outer membrane protein in , Bucl8. Here, we employed a number of bioinformatic tools to predict Bucl8-derived epitopes that are non-allergenic and non-toxic, but would elicit an immune response. From these data, we formulated a vaccine based on two extracellular components of Bucl8, the β-barrel loops and extended collagen and non-collagen domains. Outbred CD-1 mice were immunized with vaccine formulations-composed of recombinant proteins or conjugated synthetic peptides with adjuvant-to assess the antigen-specific immune responses in mouse sera and lymphoid organs. We found that mice vaccinated with either Bucl8-derived components generated a robust TH2-skewed antibody response when antigen was combined with the adjuvant AddaVax, while the TH1 response was limited. Mice immunized with synthetic loop peptides had a stronger, more consistent antibody response than recombinant protein antigens, based on higher IgG titers and recognition of bacteria. We then compared peptide-based vaccines in an established C57BL/6 inbred mouse model and observed a similar TH2-skewed response. The resulting formulations will be applied in future studies examining the protection of Bucl8-derived vaccines.
是一种在临床和生物防御方面备受关注的传染性细菌,是类鼻疽病的病原体。死亡率可达50%,每年影响16.5万人;然而,目前尚无可用疫苗。在本研究中,我们检测了对一种用源自外膜蛋白Bucl8的抗原配制的疫苗的抗原特异性免疫反应。在这里,我们使用了多种生物信息学工具来预测Bucl8衍生的表位,这些表位无致敏性且无毒,但能引发免疫反应。根据这些数据,我们基于Bucl8的两个细胞外成分,即β桶环以及延伸的胶原蛋白和非胶原蛋白结构域,配制了一种疫苗。用由重组蛋白或与佐剂结合的合成肽组成的疫苗制剂对远交系CD-1小鼠进行免疫,以评估小鼠血清和淋巴器官中的抗原特异性免疫反应。我们发现,当抗原与佐剂AddaVax结合时,用任何一种Bucl8衍生成分接种疫苗的小鼠都会产生强烈的偏向TH2的抗体反应,而TH1反应有限。基于更高的IgG滴度和对细菌的识别,用合成环肽免疫的小鼠比重组蛋白抗原产生更强、更一致的抗体反应。然后,我们在已建立的C57BL/6近交系小鼠模型中比较了基于肽的疫苗,并观察到类似的偏向TH2的反应。所得制剂将应用于未来研究Bucl8衍生疫苗的保护性研究中。