Wang Shaohui, Heuler Joshua, Bullock Jessica, Qin Junling, Chakraborty Soumyadeep, Nathaniel Agbendeh Lubem, Wang Shifeng, Sun Xingmin
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA.
Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.
Vaccines (Basel). 2024 Dec 30;13(1):21. doi: 10.3390/vaccines13010021.
BACKGROUND/OBJECTIVES: is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed cell wall protein, plays an important role in the bacterium's adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice.
we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection.
Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of vegetative cells to HCT8 cells.
Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice.
背景/目的：艰难梭菌是一种革兰氏阳性、产芽孢的肠道病原体，主要通过产生毒素引发肠道疾病，包括炎症和腹泻。艰难梭菌感染（CDI）的标准治疗方案所涉及的抗生素选择有限且效果不完全理想，导致复发率很高。疫苗接种是预防CDI及其复发的一种有前景的策略。细胞壁蛋白2（Cwp2）是一种高度免疫原性且大量暴露于表面的细胞壁蛋白，在该细菌的体外黏附中起重要作用。在本研究中，我们旨在分析Cwp2的同源性和免疫原性，以及其作为抗CDI疫苗候选物在小鼠中的保护效果。
我们进行了计算机分析以评估Cwp2的同源性和免疫原性，并使用免疫和感染小鼠模型评估其作为抗CDI疫苗候选物的潜力。
我们的计算机分析预测了Cwp2的免疫原性区域（功能域），并揭示了其在各种毒素型和核糖体分型（R.T.s）或序列分型（S.T.s）之间的高度同源性。用Cwp2功能域（Cwp2_A）免疫小鼠可诱导针对Cwp2_A的强效IgG/A抗体反应，保护小鼠免受CDI感染，并降低感染后粪便中的芽孢和毒素水平。此外，抗Cwp2_A血清可抑制营养细胞与HCT8细胞的结合。
我们的报告首次证明了Cwp2_A作为抗小鼠CDI有效疫苗候选物的潜力。
