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Haemophilus parainfluenzae is a Gram-negative opportunist pathogen within the mucus of the nose and mouth without significant symptoms and has an ability to cause various infections ranging from ear, eye, and sinus to pneumonia. A concerning development is the increasing resistance of H. parainfluenzae to beta-lactam antibiotics, with the potential to cause dental infections or abscesses. The principal objective of this investigation is to utilize bioinformatics and immuno-informatic methodologies in the development of a candidate multi-epitope Vaccine. The investigation focuses on identifying potential epitopes for both B cells (B lymphocytes) and T cells (helper T lymphocytes and cytotoxic T lymphocytes) based on high non-toxic and non-allergenic characteristics. The selection process involves identifying human leukocyte antigen alleles demonstrating strong associations with recognized antigenic and overlapping epitopes. Notably, the chosen alleles aim to provide coverage for 90% of the global population. Multi-epitope constructs were designed by using suitable linker sequences. To enhance the immunological potential, an adjuvant sequence was incorporated using the EAAAK linker. The final vaccine construct, comprising 344 amino acids, was achieved after the addition of adjuvants and linkers. This multi-epitope Vaccine demonstrates notable antigenicity and possesses favorable physiochemical characteristics. The three-dimensional conformation underwent modeling and refinement, validated through in-silico methods. Additionally, a protein-protein molecular docking analysis was conducted to predict effective binding poses between the multi-epitope Vaccine and the Toll-like receptor 4 protein. The Molecular Dynamics (MD) investigation of the docked TLR4-vaccine complex demonstrated consistent stability over the simulation period, primarily attributed to electrostatic energy. The docked complex displayed minimal deformation and enhanced rigidity in the motion of residues during the dynamic simulation. Furthermore, codon translational optimization and computational cloning was performed to ensure the reliability and proper expression of the multi-Epitope Vaccine. It is crucial to emphasize that despite these computational validations, experimental research in the laboratory is imperative to demonstrate the immunogenicity and protective efficacy of the developed vaccine. This would involve practical assessments to ascertain the real-world effectiveness of the multi-epitope Vaccine.

Streptococcus anginosus is a Gram‐positive coccus that can increase gastric cancer risk through interaction with the TMPC‐ANXA2‐MAPK axis in gastric epithelial cells. There is currently no commercially available vaccine, and prolonged antibiotic treatment may increase drug resistance. We developed a Treponema pallidum membrane protein C (TMPC)‐based multi‐epitope vaccine targeting nine TMPC‐positive streptococcal species dominated by S. anginosus. B‐cell and T‐cell epitopes were chosen based on their binding affinity, antigenicity, immunogenicity, and safety, with adjuvants and linker sequences improving construct stability and immune response. Immune simulations predicted robust humoral and cellular responses, such as cytokine production and memory cell activation. Molecular docking and molecular dynamics analysis further confirmed stable interactions between the vaccine construct and key immune receptors (HLA‐A*02:01, HLA‐DRB1*01:01, TLR2, and TLR4). The antigen was further modified as a messenger RNA vaccine to enhance cytotoxic T‐cell induction; however, animal research is needed to confirm its immunogenicity and protective effectiveness. Design process for messenger RNA vaccines. Candidate proteins are initially screened using immunoinformatics, after which selected epitopes are assembled into a multi‐epitope vaccine. The vaccine construct was evaluated through molecular docking, molecular dynamics simulations, and in silico immune simulations, followed by population coverage analysis and messenger RNA vaccine design.

Menangle Virus (MenV) is a zoonotic pathogenic virus that can penetrate humans, causing infection in them. It is an essential threat to public health due to the possibility of cross-species transmissions. Traditional vaccine development methods are time-consuming and resource-intensive, highlighting the need for innovative approaches. This study uses computational techniques to develop a multiepitope vaccine for MenV. We employed in silico tools to find potential B-cell, T-cell, and MHC-binding epitopes in the viral proteome. To ensure their safety and efficacy, these epitopes were evaluated for antigenicity, allergenicity, and toxicity. The selected epitopes were assembled into a multiepitope construct optimized for molecular stability and immunogenicity. Studies of molecular docking and MD simulations were considered to assess the interaction of vaccine candidates with human receptors, indicating a strong immune response. The goal of developing this vaccine is to prepare for potential future outbreaks. This in-silico vaccine design proposes a promising, efficient path to developing effective preventative measures against MenV, potentially expediting vaccine production and contributing to world health security.

Chlamydia trachomatis (Ct), an obligate intracellular parasite, is the leading cause of bacterial sexually transmitted diseases worldwide. The best solution to control the spread of Ct is to develop safe and effective vaccines. However, an effective vaccine has not been developed due to some challenges such as selection of appropriate candidate antigens and an effective delivery system. In our previous study, we have developed a Ct vaccine that comprises a multi-epitope peptide of Ct major outer membrane protein (MOMP370–387) and Hepatitis B virus core antigen (HBcAg). The vaccine was evaluated in a murine model with chlamydial genital infection. The results indicated that Ct MOMP multi-epitope delivered by HBcAg could be an effective vaccine for the prevention of Ct. In this study, another two epitopes were selected from the MOMP protein and tandemly linked with MOMP370–387 to enhance the immunogenicity and the protective effect of the candidate vaccine. Our results revealed that both the immunogenicity and the protective effect of the tandem Ct MOMP multi-epitopes were much better than that of the single epitope. Therefore, vaccines based on the tandem Ct MOMP multi-epitopes could be more effective immune prophylactics to prevent Ct infection than the single epitope in murine model system.

Background Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection. Results We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector. Conclusion The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world’s population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use.

Morganella morganii is one of the main etiological agents of hospital-acquired infections and no licensed vaccine is available against the pathogen. Herein, we designed a multi-epitope-based vaccine against M. morganii. Predicted proteins from fully sequenced genomes of the pathogen were subjected to a core sequences analysis, followed by the prioritization of non-redundant, host non-homologous and extracellular, outer membrane and periplasmic membrane virulent proteins as vaccine targets. Five proteins (TonB-dependent siderophore receptor, serralysin family metalloprotease, type 1 fimbrial protein, flagellar hook protein (FlgE), and pilus periplasmic chaperone) were shortlisted for the epitope prediction. The predicted epitopes were checked for antigenicity, toxicity, solubility, and binding affinity with the DRB*0101 allele. The selected epitopes were linked with each other through GPGPG linkers and were joined with the cholera toxin B subunit (CTBS) to boost immune responses. The tertiary structure of the vaccine was modeled and blindly docked with MHC-I, MHC-II, and Toll-like receptors 4 (TLR4). Molecular dynamic simulations of 250 nanoseconds affirmed that the designed vaccine showed stable conformation with the receptors. Further, intermolecular binding free energies demonstrated the domination of both the van der Waals and electrostatic energies. Overall, the results of the current study might help experimentalists to develop a novel vaccine against M. morganii.

The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL and then docked with different toll-like-receptors (TLR4, TLR7, and TLR8) using PatchDock, HADDOCK, and FireDock, respectively. From the overlapped epitopes, we designed five vaccine constructs C1–C5. Based on antigenicity, allergenicity, solubility, different physiochemical properties, and molecular docking scores, we selected the vaccine construct 1 (C1) for further processing. Docking of C1 with TLR4, TLR7, and TLR8 showed striking interactions with global binding energy of −43.48, −65.88, and −60.24 Kcal/mol, respectively. The docked complex was further simulated, which revealed that both molecules remain stable with minimum RMSF. Activation of TLRs induces downstream pathways to produce pro-inflammatory cytokines against viruses and immune system simulation shows enhanced antibody production after the booster dose. In conclusion, C1 was the best vaccine candidate among all designed constructs to elicit an immune response SARS-CoV-2 and combat the coronavirus disease (COVID-19).

Background Norovirus (NoVs) is a foodborne pathogen that causes acute gastroenteritis. The diversity of its principal antigenic protein poses a significant challenge to vaccine development and the prevention of large-scale outbreaks globally. Currently, no licensed vaccines against norovirus have been approved. Methods We developed a novel pipeline that integrates multiple bioinformatics tools to design broad-spectrum vaccines against NoVs. Specifically, broad-spectrum T-cell epitope vaccines were designed based on consensus sequences and optimized epitope screening, while broad-spectrum B-cell spatial epitope vaccines were constructed using high-throughput antigenicity calculations and epitope mapping. Results This pipeline underwent rigorous validation at three levels: firstly, In silico validation: Analysis of properties and structures demonstrated the appropriateness of amino acid composition and the structural integrity of the vaccine sequences. Secondly, theoretical assessment: Evaluation of human leukocyte antigen (HLA) subtype and antigenicity coverage indicated a broad theoretical protective spectrum for the designed vaccine immunogens. Furthermore, in silico simulation confirmed their ability to elicit an immune response. Finally, animal-level validation: Experiments in mice showed that both vaccine immunogens stimulated high levels of IgG and IgA. Notably, Vac-B induced a strong IgG response against GII.2 and a robust IgA response against GII.17, comparable to the immune response elicited by the wild-type NoV non-replicating virus-like particle (VLP) protein group. Conclusions Both in silico and in vivo experimental findings suggest that the proposed pipeline and vaccine immunogens could serve as valuable theoretical guidance for the development of multi-epitope vaccines against NoVs.

Graphical Abstract Highlight Research The study aims to develop a multi-epitope vaccine (MEV) against A. hydrophila by targeting the aerolysin toxin, a key virulence factor responsible for infections in fish and humans. Computational methods identified and optimized B-cell and T-cell epitopes, focusing on their ability to trigger immune responses without causing toxicity or allergenicity. In silico simulations demonstrated that the MEV has a strong binding affinity to immune receptors like TLR-4, MHC-I, and MHC-II, indicating its potential to induce robust cellular and humoral immunity. Structural analysis of the MEV showed a stable 3D conformation, with most residues in favorable regions, ensuring stability during immune activation. The MEV could enhance disease control in aquaculture and reduce human infection risks, offering a promising solution to address antibiotic resistance and the absence of effective vaccines. Abstract Aeromonas hydrophila, gram-negative, is a major pathogen responsible for various diseases in mammals, reptiles, amphibia, and vertebrates, including fish and humans. Targeting the specific toxin aerolysin in A. hydrophila is crucial to address antibiotic resistance and the lack of adequate and protective vaccines against this intracellular pathogen. This study aimed to identify a multi-epitope vaccination (MEV) candidate targeting A. hydrophila aerolysin toxin to combat the disease effectively. Standard biochemical characterization methods and sequencing of the 16S rRNA, rpoB, and aerA genes identified the isolate AHSA1 as A. hydrophila. Subsequently, we identified B and T cell epitopes on the aerolysin protein and separately predicted MHC-I and MHC-II epitopes. The epitopes are then evaluated for toxicity, antigenicity, allergenicity, and solubility. The vaccine design integrated multi-epitope-based constructs, utilizing specialized linkers (GPGPG) and EAAAK linkers to connect epitope peptides with adjuvants in the cholera toxin B component, thereby enhancing immunogenicity. Ramachandran plots showed that 85.25% of the residues were located in the most favorable regions, which was followed by the generously allowed zone (1.30%), the additional allowed regions (10.80%), and the forbidden regions (2.65%), thus confirming the feasibility of the modeled vaccine design. Based on docking simulations, MEV had the highest binding and interaction energies with TLR-4, TLR-9, MHC-I, and MHC-II (-1081.4, -723.2, 866.2, -9043.3 kcal/mol). Based on computational modelling, we expect the Aerolysin MEV candidate design to activate diverse immune mechanisms, stimulate robust responses against A. hydrophila, and maintain safety. The significant solubility, absence of toxicity or allergic response, and minimal side effects in animal testing all contribute to the potential clinical utility of this vaccine candidate.  

The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this major health issue. Leptotrichia buccalis is a Gram-negative, rod-shaped bacterium which normally resides in the oral and vaginal cavities. It is an emerging bacterial pathogen which is developing new antibiotic-resistance mechanisms. No approved vaccine is available against this pathogen, which is a cause for growing concern. In this study, an in silico-based, multi-epitopes vaccine against this pathogen was designed by applying reverse vaccinology and immunoinformatic approaches. Of a total of 2193 predicted proteins, 294 were found to be redundant while 1899 were non-redundant. Among the non-redundant proteins, 6 were predicted to be present in the extracellular region, 12 in the periplasmic region and 23 in the outer-membrane region. Three proteins (trypsin-like peptidase domain-containing protein, sel1 repeat family protein and TrbI/VirB10 family protein) were predicted to be virulent and potential subunit vaccine targets. In the epitopes prediction phase, the three proteins were subjected to B- and T-cell epitope mapping; 19 epitopes were used for vaccine design. The vaccine construct was docked with MHC-I, MHC-II and TLR-4 immune receptors and only the top-ranked complex (based on global energy value) was selected in each case. The selected docked complexes were examined in a molecular dynamic simulation and binding free energies analysis in order to assess their intermolecular stability. It was observed that the vaccine binding mode with receptors was stable and that the system presented stable dynamics. The net binding free energy of complexes was in the range of −300 to −500 kcal/mol, indicating the formation of stable complexes. In conclusion, the data reported herein might help vaccinologists to formulate a chimeric vaccine against the aforementioned target pathogen.