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. 2021 Jun 18;9(6):669.
doi: 10.3390/vaccines9060669.

In Silico Prediction of a Multitope Vaccine against Moraxella catarrhalis: Reverse Vaccinology and Immunoinformatics

Affiliations

In Silico Prediction of a Multitope Vaccine against Moraxella catarrhalis: Reverse Vaccinology and Immunoinformatics

Mohamed A Soltan et al. Vaccines (Basel). .

Abstract

Moraxella catarrhalis (M. catarrhalis) is a Gram-negative bacterium that can cause serious respiratory tract infections and middle ear infections in children and adults. M. catarrhalis has demonstrated an increasing rate of antibiotic resistance in the last few years, thus development of an effective vaccine is a major health priority. We report here a novel designed multitope vaccine based on the mapped epitopes of the vaccine candidates filtered out of the whole proteome of M. catarrhalis. After analysis of 1615 proteins using a reverse vaccinology approach, only two proteins (outer membrane protein assembly factor BamA and LPS assembly protein LptD) were nominated as potential vaccine candidates. These proteins were found to be essential, outer membrane, virulent and non-human homologs with appropriate molecular weight and high antigenicity score. For each protein, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell lymphocyte (BCL) epitopes were predicted and confirmed to be highly antigenic and cover conserved regions of the proteins. The mapped epitopes constituted the base of the designed multitope vaccine where suitable linkers were added to conjugate them. Additionally, beta defensin adjuvant and pan-HLA DR-binding epitope (PADRE) peptide were also incorporated into the construct to improve the stimulated immune response. The constructed multitope vaccine was analyzed for its physicochemical, structural and immunological characteristics and it was found to be antigenic, soluble, stable, non-allergenic and have a high affinity to its target receptor. Although the in silico analysis of the current study revealed that the designed multitope vaccine has the ability to trigger a specific immune response against M. catarrhalis, additional translational research is required to confirm the effectiveness of the designed vaccine.

Keywords: Moraxella catarrhalis; epitope mapping; immunoinformatics; multitope vaccine; reverse vaccinology; vaccinomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of applied filtration steps for the nomination of potential vaccine candidates by applying reverse vaccinology technique.
Figure 2
Figure 2
Protein–protein interaction network of vaccine candidates, estimated by STRING database.
Figure 3
Figure 3
Secondary structure prediction of designed multitope vaccine using PESIPRED server.
Figure 4
Figure 4
Structural analysis of the designed vaccine. (A) The three-dimensional structure of the vaccine obtained after molecular refinements; (B) ProSA-web evaluation of the vaccine structure; (C) Ramachandran plot analysis of the protein structure after molecular refinements.
Figure 5
Figure 5
Docked complex of vaccine construct (red) with human TLR2 (green).
Figure 6
Figure 6
Molecular dynamics simulation of multitope vaccine–TLR2 complex; stability of the protein–protein complex was investigated through B-factor values (A), deformability (B), variance (C), eigenvalue (D), covariance of residue index (E) and elastic network (F) analysis.

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