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. 2022 Sep 17:2022:4975721.
doi: 10.1155/2022/4975721. eCollection 2022.

Vaccinomics to Design a Multiepitope Vaccine against Legionella pneumophila

Ahitsham Umar  1 , Sadia Liaquat  1 , Israr Fatima  1 , Abdur Rehman  1 , Danish Rasool  1 , Abdulrahman Alshammari  2 , Metab Alharbi  2 , Muhammad Shahid Riaz Rajoka  3 , Mohsin Khurshid  4 , Usman Ali Ashfaq  1 , Asma Haque  1
Affiliations

Vaccinomics to Design a Multiepitope Vaccine against Legionella pneumophila

Ahitsham Umar et al. Biomed Res Int. .

Abstract

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.

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Conflict of interest statement

The authors report no conflicts of interest for this work.

Figures

Figure 1
Figure 1
Worldwide population coverage analysis of selected epitopes.
Figure 2
Figure 2
Constructed vaccine figure with adjuvants and linkers. Each color represents the specific linker.
Figure 3
Figure 3
(a–c) Vaccine construct sequence along with predicted structure and structure evaluation analysis: (a) depicts the sequence of the vaccine after addition of different linkers and an adjuvant; (b) is the predicted structure of the vaccine using I-TASSER server; (c) describes the conformational analysis of the structure, and the red zones in that plot indicated the favored regions and the number of residues in it.
Figure 4
Figure 4
Docked complex of TLR4 construct with the vaccine construct indicating the interacting part along with the interacting residue. The red part is for the vaccine, and the purple is for theTLR4 in this docking.
Figure 5
Figure 5
Interaction of vaccine construct with MHC-I construct. The red part is of the vaccine, and the green one is indicating the MHC-I construct; clashes and contacts are also given.
Figure 6
Figure 6
Interaction of vaccine construct with MHC-II construct. The blue part depicts the MHC-II and clashes, and contacts are given on the right side of the figure.
Figure 7
Figure 7
(a–e) Molecular dynamic simulation of the vaccine-TLR4 complex, showing (a) eigenvalue, (b) deformability, (c) B-factor, (d) covariance matrix, and (e) elastic network analysis.
Figure 8
Figure 8
(a, b) In silico immune responses of vaccine as an antigen: (a) immunoglobulin generation and B cell isotypes following exposure in different states with the Simpson index to the antigen; (b) development of cytokine and interleukins.
Figure 9
Figure 9
In silico cloning of codon-optimized vaccine into E. coli K12 expression system. The plasmid backbone is kept in black while the inserted DNA sequence is shown in red color.
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