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.
Highlights
M. catarrhalis is known to be a human-restricted commensal, but studies in recent decades have proved that it has become a major infectious agent in both the upper and lower respiratory tract and the causative agent of about 17% of acute otitis media infections in children [1]
The flow of work started with the application of the reverse vaccinology approach to select which proteins would be our vaccine candidates, B and T cell epitopes were mapped for these candidates and, following that, the multitope vaccine was constructed and, it was analyzed for its physicochemical, structural and immunological characteristics
Virulence assessment of these proteins revealed that only LPS assembly protein LptD and outer membrane protein assembly factor BamA were virulent, other protein filtration steps were performed only for these proteins (Figure 1) where analysis results (Table 1) confirmed their nomination as potential vaccine candidates of the current study
Summary
M. catarrhalis is known to be a human-restricted commensal, but studies in recent decades have proved that it has become a major infectious agent in both the upper and lower respiratory tract and the causative agent of about 17% of acute otitis media infections in children [1]. Usage of antibiotics without restrictions has contributed largely to the development of resistant bacterial strains which in turn shorten the list of available effective antimicrobial agents [3]. Adhesive proteins of M. catarrhalis were extensively targeted as potential vaccine candidates. They are outer membrane proteins that allow the microorganism to bind to its target receptor in the human respiratory tract, which is the first step in bacterial pathogenesis [5]. Application of this vaccine in animal models showed an enhanced lung clearance of bacteria [6]
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