Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium

Abstract

Mycoplasma genitalium, besides urethritis, causes a number of other sexually transmitted diseases, posing a significant health threat to both men and women, particularly in developing countries. In light of the rapid appearance of multidrug-resistant strains, M. genitalium is regarded as an emerging threat and has been placed on the CDC’s “watch list”. Hence, a protective vaccine is essential for combating this pathogen. In this study, we utilized reverse vaccinology to develop a chimeric vaccine against M. genitalium by identifying vaccine targets from the reference proteome (Strain G-37) of this pathogen. A multiepitope vaccine was developed using proteins that are non-toxic, non-allergic, and non-homologous to human proteins. Several bioinformatic tools identified linear and non-linear B-cell epitopes, as well as MHC epitopes belonging to classes I and II, from the putative vaccine target proteins. The epitopes that showed promiscuity among the various servers were shortlisted and subsequently selected for further investigation based on an immunoinformatic analysis. Using GPGPG, AAY, and KK linkers, the shortlisted epitope sequences were assembled to create a chimeric construct. A GPI anchor protein immunomodulating adjuvant was adjoined to the vaccine construct’s N-terminus through the EAAK linker so as to improve the overall immunogenicity. For further investigations of the designed construct, various bioinformatic tools were employed to study the physicochemical properties, immune profile, solubility, and allergenicity profile. A tertiary chimeric design was computationally modeled using I-TASSER and Robetta and was subsequently refined through GalaxyRefine. ProSA-Web was exploited to corroborate the quality of the construct by detecting errors and the Ramachandran plot was used to identify possible quality issues. Simulation studies of the molecular dynamics demonstrated the robustness and flexibility of the designed construct. Following the successful docking of the designed model to the immune receptors, the construct was computationally cloned into Escherichia coli plasmids to affirm the efficient expression of the designed construct in a biological system.

Designing a multiepitope mRNA- based vaccine against Enterotoxigenic Escherichia coli infection in calves: Immuno-informatics and molecular modelling approach

“…Several researchers suggested the vaccine policy to be a global strategy in combatting multidrug-resistant bacteria. However, hypersensitivity is one of the major limitations of traditional vaccines that are designed with large proteins ( Khalid et al ., 2022 ; Islam et al ., 2022 ; Jalal et al ., 2023 ). Compared to traditional vaccines, multiepitope using reverse vaccinology is a new vaccine approach with a lot of advantages including strong stimulation of cellular and humoral immune response, low-cost production, and high specificity and safety ( Hashish et al ., 2013 ; Feuerstein et al ., 2022 ; Sanami et al ., 2023 ).…”

Cryo-electron tomography reveals the binding and release states of the major adhesion complex from Mycoplasma genitalium

“…While mycoplasma are typically extracellular pathogens, they can also invade host cells, which is thought to be a critical step in chronification [9,10]. No approved vaccines are currently available [11], and given the natural resistance of mycoplasma to cell wall antibiotics, macrolides (antibiotics inhibiting protein synthesis) have been most commonly used to treat mycoplasma infections [12]. In the last years, however, an increased prevalence of macrolide-resistant mycoplasma infections has been reported [13].…”