Klebsiella aerogenes 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 K. aerogenes 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 K. aerogenes. 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.
24 March 2023 in World Journal of Microbiology and Biotechnology
Legionella pneumophila is found in the natural aquatic environment and can resist a wide range of environmental conditions. There are around fifty species of Legionella, at least twenty‐four of which are directly linked to infections in humans. L. pneumophila is the cause of Legionnaires’ disease, a potentially lethal form of pneumonia. By blocking phagosome‐lysosome fusion, L. pneumophila lives and proliferates inside macrophages. For this disease, there is presently no authorized multiepitope vaccine available. For the multi‐epitope‐based vaccine (MEBV), the best antigenic candidates were identified using immunoinformatics and subtractive proteomic techniques. Several immunoinformatics methods were utilized to predict B and T cell epitopes from vaccine candidate proteins. To construct an in silico vaccine, epitopes (07 CTL, 03 HTL, and 07 LBL) were carefully selected and docked with MHC molecules (MHC‐I and MHC‐II) and human TLR4 molecules. To increase the immunological response, the vaccine was combined with a 50S ribosomal adjuvant. To maximize vaccine protein expression, MEBV was cloned and reverse‐translated in Escherichia coli. To prove the MEBV’s efficacy, more experimental validation is required. After its development, the resulting vaccine is greatly hoped to aid in the prevention of L. pneumophila infections.