Peptostreptococcus anaerobius is an anaerobic bacterium,which has been found selectively en-riched in the fecal and mucosal microbiota of colorectal cancer(CRC)patients.Emerging evidence suggest P.anaerobius may contr...Peptostreptococcus anaerobius is an anaerobic bacterium,which has been found selectively en-riched in the fecal and mucosal microbiota of colorectal cancer(CRC)patients.Emerging evidence suggest P.anaerobius may contribute to the development of CRC in human.In this study,we designed a multi-epitope chimeric vaccine against P.anaerobius PCWBR2,a recently identified adhesin that interacts directly with colon cell lines by bindingα2/β1 integrin frequently overexpressed in human CRC tumors and cell lines.Immunoinformatics tools predicted six cytotoxic T lymphocyte epitopes,five helper T lymphocyte epitopes,and six linear B lymphocyte epitopes.The predicted epitopes were joined with AAY or GPGPG linkers and a previously reported TLR4 agonist was added to the vaccine construct’s N terminal as an adjuvant using EAAAK linkers and the order of epitopes was optimized.Further in silico analysis revealed that the vaccine construct possesses satisfactory antigenicity,allergenicity,solubility,physicochemical properties,adjuvant-TLR4 molecular docking,and immune profile characteristics.Our study provided a promising design for vaccines against P.anaerobius.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2020YFA0907800)the National Natural Science Foundation of China(Grant No.32000096)+2 种基金the Shenzhen Science and Technology Innovation Program(KQTD20200820145822023)the Program of Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases(ZDSYS20220606100803007)the Foshan Science and Technology Innovation Program(2120001010795).
文摘Peptostreptococcus anaerobius is an anaerobic bacterium,which has been found selectively en-riched in the fecal and mucosal microbiota of colorectal cancer(CRC)patients.Emerging evidence suggest P.anaerobius may contribute to the development of CRC in human.In this study,we designed a multi-epitope chimeric vaccine against P.anaerobius PCWBR2,a recently identified adhesin that interacts directly with colon cell lines by bindingα2/β1 integrin frequently overexpressed in human CRC tumors and cell lines.Immunoinformatics tools predicted six cytotoxic T lymphocyte epitopes,five helper T lymphocyte epitopes,and six linear B lymphocyte epitopes.The predicted epitopes were joined with AAY or GPGPG linkers and a previously reported TLR4 agonist was added to the vaccine construct’s N terminal as an adjuvant using EAAAK linkers and the order of epitopes was optimized.Further in silico analysis revealed that the vaccine construct possesses satisfactory antigenicity,allergenicity,solubility,physicochemical properties,adjuvant-TLR4 molecular docking,and immune profile characteristics.Our study provided a promising design for vaccines against P.anaerobius.