Umar Ahitsham, Haque Asma, Alghamdi Youssef Saeed, Mashraqi Mutaib M, Rehman Abdur, Shahid Farah, Khurshid Mohsin, Ashfaq Usman Ali
Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Department of Biology, Turabah University College, Taif University, Taif 21944, Saudi Arabia.
Vaccines (Basel). 2021 Nov 22;9(11):1373. doi: 10.3390/vaccines9111373.
is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, which confer high resistance. The drug resistance in has been reported in China, Israel, Poland, Italy and the United States, with a high mortality rate (~50%). This study aims to combine immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against . The synthesis of the B-cell, T-cell (CTL and HTL) and IFN-γ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies. The vaccine was predicted by connecting the respective epitopes, i.e., B cells, CTL and HTL with KK, AAY and GPGPG linkers and all these were connected with N-terminal adjuvants with EAAAK linker. The humoral response of the constructed vaccine was measured through IFN-γ and B-cell epitopes. Before being used as vaccine candidate, all identified B-cell, HTL and CTL epitopes were tested for antigenicity, allergenicity and toxicity to check the safety profiles of our vaccine. To find out the compatibility of constructed vaccine with receptors, MHC-I, followed by MHC-II and TLR4 receptors, was docked with the vaccine. Lastly, in order to precisely certify the proper expression and integrity of our construct, in silico cloning was carried out. Further studies are needed to confirm the safety features and immunogenicity of the vaccine.
是一种革兰氏阴性菌,近年来其重要性日益凸显。它与10%的医院获得性和社区获得性尿路感染以及12%的医院获得性肺炎有关。这种微生物具有产生诱导型染色体AmpCβ-内酰胺酶的内在能力,这赋予了其高度耐药性。在中国、以色列、波兰、意大利和美国均已报道了该菌的耐药情况,死亡率很高(约50%)。本研究旨在将免疫学方法与分子对接方法相结合,针对三种高抗原性蛋白设计针对该菌的疫苗。对目标蛋白的B细胞、T细胞(CTL和HTL)以及IFN-γ表位进行了合成,并选择了最保守的表位用于未来的研究。通过将各自的表位,即B细胞、CTL和HTL与KK、AAY和GPGPG接头连接来预测疫苗,并且所有这些都通过EAAAK接头与N端佐剂相连。通过IFN-γ和B细胞表位来检测构建疫苗的体液反应。在用作候选疫苗之前,对所有鉴定出的B细胞、HTL和CTL表位进行抗原性、致敏性和毒性测试,以检查我们疫苗的安全性。为了确定构建疫苗与受体的兼容性,将MHC-I,随后是MHC-II和TLR4受体与疫苗进行对接。最后,为了精确验证我们构建体的正确表达和完整性,进行了电子克隆。需要进一步研究来确认疫苗的安全性和免疫原性。