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The emerging monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes infections in humans similar to smallpox. Since May 2022, cases of monkeypox (MPX) have been increasingly reported by the World Health Organization (WHO) worldwide. Currently, there are no clinically validated treatments for MPX infections. In this study, an immunoinformatics approach was used to identify potential vaccine targets against MPXV. A total of 190 MPXV-2022 proteins were retrieved from the ViPR database and subjected to various analyses including antigenicity, allergenicity, toxicity, solubility, IFN-γ, and virulence. Three outer membrane and extracellular proteins were selected based on their respective parameters to predict B-cell and T-cell epitopes. The epitopes are conserved among different strains of MPXV and the population coverage is 100% worldwide, which will provide broader protection against various strains of the virus globally. Nine overlapping MHC-I, MHC-II, and B-cell epitopes were selected to design multi-epitope vaccine constructs linked with suitable linkers in combination with different adjuvants to enhance the immune responses of the vaccine constructs. Molecular modeling and structural validation ensured high-quality 3D structures of vaccine constructs. Based on various immunological and physiochemical properties and docking scores, MPXV-V2 was selected for further investigation. In silico cloning revealed a high level of gene expression for the MPXV-V2 vaccine within the bacterial expression system. Immune and MD simulations confirmed the molecular stability of the MPXV-V2 construct, with high immune responses within the host cell. These results may aid in the development of experimental vaccines against MPXV with increased potency and improved safety.

The monkeypox virus ( MPXV ) is a newly discovered zoonotic orthopoxvirus that can infect humans and shares similarities with the smallpox virus . With no clinically validated treatment for MPXV infections, it is important to develop a broad-range vaccine that is effective against this disease. This study aimed to design novel multiple-epitope DNA and mRNA vaccines against MXPV using comprehensive immunoinformatics and reverse vaccinology techniques. Eleven MPXV proteins were selected from the UniProt database and assessed for their antigenicity and allergenicity. Proteins exhibiting significant antigenicity and non-allergenic characteristics were examined for the prediction of T-cell and B-cell epitopes. Four MHC-I, eight MHC-II, and six B-cell epitopes were coupled with specific linkers and adjuvant peptide sequences to boost the immunological response to the developed vaccine. The designed vaccines showed antigenic nature with a 0.5936 score and solubility nature with a 0.513 score, and its GRAVY score of 0.147 indicates their hydrophilic nature. Structural validation confirmed the superior tertiary structure of the designed vaccines. Molecular docking studies demonstrated a robust interaction between human TLR-8 and the developed vaccines, with a docking score of -1208.2 kcal/mol, and Moleculae Dynamics (MD) simulations confirmed its stability. The immune simulation results indicated that vaccination strongly stimulated immunity, resulting in high concentrations of IgG and IgM antibodies. Cloning analysis and in silico restriction prediction demonstrated the viability of integrating the developed vaccine into an Escherichia coli ( E. coli) expression system. Furthermore, an mRNA vaccine was developed by incorporating a 5′ cap, 5′ untranslated region (UTR), Kozak sequence, and tissue plasminogen activator (tPA) with the CD40 ligand (CD40L) linked to the selected epitopes using EAAAK linkers. A poly (A) tail, MITD1, and 3′ UTR were appended to the 3′ end of the construct. The mRNA vaccine design incorporated codon optimization, resulting in a CAI score 0.83 and GC content of 60.46%, indicating efficient vaccine expression within host cells. Analysis of several parameters revealed that the architecture of the synthesized mRNA was stable with MFE: -2170.70 kcal/mol. These outcomes may contribute to the development of an experimental MPXV vaccine with stronger potency and superior safety measures. Additional in vitro and in vivo experiments are required to test the safety and efficacy of these newly developed vaccines. Highlights MPXV proteins were selected and assessed for safety and efficacy as potential vaccine targets. Four MHC-I, eight MHC-II, and six B-cell epitopes were identified and combined with an adjuvant to design the final vaccine. The vaccine demonstrated favorable interactions with human TLR-8 and exhibited good stability. The experimental results demonstrated a significant enhancement in the immune response, characterized by increased levels of IgG and IgM. An mRNA vaccine was developed with specific sequences to improve cellular efficacy, with a GC content of 60.46%. Both protein-based and mRNA vaccines have shown promising results in laboratory tests.

The increasing and ongoing issue of antibiotic resistance in bacteria is of huge concern globally, mainly to healthcare facilities. It is now crucial to develop a vaccine for therapeutic and preventive purposes against the bacterial species causing hospital-based infections. Among the many antibiotic- resistant bacterial pathogens, the Enterobacter cloacae complex (ECC) including six species, E. Colcae , E. absuriae , E. kobie, E. hormaechei, E. ludwigii , and E. nimipressuralis , are dangerous to public health and may worsen the situation. Vaccination plays a vital role in the prevention of infections and infectious diseases. This research highlighted the construction and design of a multi-epitope vaccine for the E. cloacae complex by retrieving their complete sequenced proteome. The retrieved proteome was assessed to opt for potential vaccine candidates using immunoinformatic tools. Both B and T-cell epitopes were predicted in order to create both humoral and cellular immunity and further scrutinized for antigenicity, allergenicity, water solubility, and toxicity analysis. The final potential epitopes were subjected to population coverage analysis. Major histocompatibility complex (MHC) class combined, and MHC Class I and II world population coverage was obtained as 99.74%, and 98.55% respectively while a combined 81.81% was covered. A multi-epitope peptide-based vaccine construct consisting of the adjuvant, epitopes, and linkers was subjected to the ProtParam tool to calculate its physiochemical properties. The total amino acids were 236, the molecular weight was 27.64kd, and the vaccine construct was stable with an instability index of 27.01. The Grand Average of Hydropathy (GRAVY) (hydrophilicity) value obtained was -0.659, being more negative and depicting the hydrophilic character. It was non-allergen antigenic with an antigenicity of 0.8913. The vaccine construct was further validated for binding efficacy with immune cell receptors MHC-I, MHC-II, and Toll-like receptor (TLR)-4. The molecular docking results depict that the designed vaccine has good binding potency with immune receptors crucial for antigen presentation and processing. Among the Vaccine-MHC-I, Vaccine-MHC-II, and Vaccine-TLR-4 complexes, the best-docked poses were identified based on their lowest binding energy scores of -886.8, -995.6, and -883.6, respectively. Overall, we observed that the designed vaccine construct can evoke a proper immune response and the construct could help experimental researchers in the formulation of a vaccine against the targeted pathogens.

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.

Small cell lung cancer (SCLC) is one of the most common cancers and it is the sixth common cause for cancer-related deaths. The high plasticity and metastasis have been a major challenge for humanity to treat the disease. Hence, a vaccine for SCLC has become an urgent need of the hour due to public health concern. Implementation of immunoinformatics technique is one of the best way to find a suitable vaccine candidate. Immunoinformatics tools can be used to overcome the limitations and difficulties of traditional vaccinological techniques. Multi-epitope cancer vaccines have become a next-generation technique in vaccinology which can be used to stimulate more potent immune response against a particular antigen by eliminating undesirable molecules. In this study, we used multiple computational and immunoinformatics approach to design a novel multi-epitope vaccine for small cell lung cancer. Nucleolar protein 4 (NOL4) is an autologous cancer-testis antigen overexpressed in SCLC cells. Seventy-five percent humoral immunity have been identified for this particular antigen. In this study, we mapped immunogenic cytotoxic T lymphocyte, helper T lymphocyte, and interferon-gamma epitopes present in NOL4 antigen and designed a multi-epitope-based vaccine using the predicted epitopes. The designed vaccine was antigenic, non-allergenic, and non-toxic with 100% applicability on human population. The chimeric vaccine construct showed stable and significant interaction with endosomal and plasmalemmal toll-like receptors in molecular docking and protein–peptide interaction analysis, thus assuring a strong potent immune response against the vaccine upon administration. Therefore, these preliminary results can be used to carry out further experimental investigations.

There is no vaccine for severe malaria. STEVOR antigens on the surface of -infected red blood cells are implicated in severe malaria and are targeted by neutralizing antibodies, but their epitopes remain unknown. Using computational immunology, we identified highly immunogenic overlapping B- and T-cell epitopes (referred to as multiepitopes, 7-27 amino acids) in the semiconserved domain of four STEVORs linked with severe malaria and clinical immunity. Structural analyses confirmed the conservation in homologous sequences across 138 clinical isolates (Togo and Brazil) and 342 global strains. Designed fused multiepitopes showed high IgG antibody reactivity in the sera of . -infected individuals. The fused multiepitopes had no allergenicity/toxicity, and phenotyping via flow cytometry and immunological assays revealed the induction of CD4+ and CD8+ T-cell proliferation and IgG antibodies in BALB/c mice, respectively. On this basis, structure-guided design of a multiepitope fusion antigen (MEFA) vaccine construct achieved 97.15% global combined HLA coverage and elicited both cellular and humoral immunity . Recombinant MEFA was stably expressed in and recognized significantly more anti-STEVOR IgG antibodies in the sera of nonsevere malaria cases than in those of severe cases, underscoring its potential immunogenicity and association with milder disease. The STEVOR MEFA construct emerges as a promising severe malaria vaccine candidate, combining global HLA coverage, safety, and broad immunogenicity linked to milder clinical outcomes.

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multi-epitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of −329.46 (kcal/mol) for TLR-3 and −358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety.

Lassa fever, caused by the Lassa virus (LASV), remains a major public health threat in West Africa, characterized by recurrent outbreaks, high mortality rates, and significant socio-economic impact. The lack of a licensed vaccine and challenges of traditional vaccine development for this Biosafety Level 4 pathogen call for innovative, safe, and effective approach to identify vaccine candidates against LASV. In this study, an integrated reverse vaccinology approach was employed to design a multi-epitope subunit vaccine targeting the conserved L protein of LASV. Linear and conformational B-cell epitopes, cytotoxic T-lymphocyte (CTL; MHC-I) epitopes, and helper T-lymphocyte (HTL; MHC-II) epitopes were predicted using established servers. The epitopes were rigorously filtered and assembled into a chimeric vaccine construct using appropriate linkers and an N-terminal adjuvant. The construct was evaluated and predicted to be antigenic, non-allergenic, hydrophilic, and soluble. Structural modelling and validation confirmed good physicochemical properties of the vaccine candidate. Docking revealed stable interaction with TLR4; immune simulation predicted robust activation of CD4 + and CD8 + T-cells, a Th1-polarized cytokine profile (IFN-γ, IL-2), and a lasting memory response; while population coverage analysis indicated broad global and West African coverage. The vaccine construct targets cell-mediated immunity critical for protection against LASV while its unique sequence features suggest potential self-adjuvanting properties. While its predicted instability may require formulation strategies, the vaccine construct demonstrates strong preclinical promise. Hence, it was concluded that the vaccine is represent a novel and computationally validated multi-epitope candidate designed LASV to elicit potent and durable immune responses, providing a solid foundation for downstream experimental evaluation.

Background Acinetobacter baumannii, a nosocomial pathogen, has emerged as a major clinical threat due to its ability to resist a broad range of antibiotics, contributing to the increased morbidity and mortality in hospital settings. This characteristic of Acinetobacter baumannii as a multiple-drug resistant (MDR) organism poses a critical global health challenge, necessitating an urgent need for alternative therapeutic strategies, such as vaccine development, as a preventive measure. In this study, we employ the method of reverse vaccinology and immunoinformatic tools to design a novel rRNA-based vaccine targeting the 16S and 23S rRNA of Acinetobacter baumannii. Results 16S and 23S rRNA sequences of Acinetobacter baumannii were retrieved from the National Center for Biotechnology Information database (NCBI). The B and T cells’ epitopes were predicted from these retrieved sequences using bioinformatics tools. The epitopes generated were further analyzed for antigenicity, toxicity, and allergenicity. The epitopes that passed these screenings, including key structural elements, were used in the design of the vaccine. The vaccine constructs were further assessed for their physicochemical properties and dynamics. Structural modeling and molecular docking studies confirmed effective binding to Toll-like receptor 4 (TLR-4), while immune simulations demonstrated the potential to elicit robust and durable immune responses. Conclusions This study demonstrates the potential of reverse vaccinology and immunoinformatics approaches in designing a novel rRNA-based vaccine targeting the 16S and 23S rRNA of Acinetobacter baumannii . By identifying highly antigenic, non-toxic, and non-allergenic epitopes and incorporating them into a structurally optimized rRNA-based vaccine construct, we present a promising candidate capable of eliciting strong immune responses. However, limitations such as the unavailability of datasets, especially on the 5S rRNA region in the databases, are a roadblock that needs to be addressed.

Tick-borne encephalitis virus (TBEV), belonging to the Flaviviridae family, is transmitted to humans via infected tick bites, leading to serious neurological complications and, in some cases, death. The available vaccines against the TBEV are reported to have low immunogenicity and are associated with adverse effects like swelling, redness and fever. Moreover, these vaccines are whole-organism-based, carry a risk of reactivation and potential for significant mortality. Consequently, to design a potential antigenic and non-allergenic multi-epitope subunit vaccine against the TBEV, we used an immunoinformatic approach to screen the Tick-borne virus proteome for highly antigenic CTL, HTL and B cell epitopes. The proper folding of the constructed vaccine was validated by a molecular dynamic simulation. Additionally, the molecular docking and binding free energy (−87.50 kcal/mol) further confirmed the strong binding affinity of the constructed vaccine with TLR-4. The vaccine exhibited a CAI value of 0.93 and a GC content of 49%, showing a high expression capability in E coli. Moreover, the analysis of immune simulation demonstrated robust immune responses against the injected vaccine and clearance of the antigen with time. In conclusion, our vaccine candidate shows promise for both in vitro and in vivo analyses due to its high immunogenicity, non-allergenicity and stable interaction with the human TLR-4 receptor.