RESUMEN

Introduction: The current vaccine strategies to prevent cervical cancer are effective only for individuals unexposed to HPV, lacking therapeutic effects against pre-existing infections. Multiepitope vaccines, using an immunoinformatic approach, are promising against tumors and viral infections because of their high specificity, safety, and stability, as well as the cheap cost of development. Methods: This study employed computer-based immunoinformatic analysis to design therapeutic multiepitope vaccines against cervical cancer using oncoproteins E6 and E7 of HPV 16 and 18. Several immunoinformatic tools were applied to analyze potential vaccine constructs capable of stimulating immune responses against both oncoproteins. Results: The constructed vaccine exhibited antigenic, immunogenic, nonallergenic, nontoxic, stable, and soluble characteristics. Additionally, it effectively interacted with TLR2 and TLR4, showing high binding capacity. Computational analysis indicated the vaccine could induce immune responses through the elevation of cytokine levels after the third injection, antibody production, activation of memory B and T cells, and promotion of increased dendritic cell counts. Conclusion: The novel multiepitope vaccine based on E6 and E7 presented as a promising candidate for combating HPV infections and associated cervical cancer. Further in vitro and in vivo studies were essential to validate the efficacy and safety of the vaccine.

RESUMEN

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.

Asunto(s)

RESUMEN

Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.

Asunto(s)

RESUMEN

Simultaneous targeting of several mutations can be useful in colorectal cancer (CRC) due to its heterogeneity and presence of somatic mutations. As CT26 mutations and expression profiles resemble those of human CRC, we focused on designing a polyepitope vaccine based on CT26 neoepitopes. Due to its low immunogenicity, outer membrane vesicles (rOMV) as an antigen delivery system and adjuvant was applied. Herein, based on previous experimental and our in silico studies four CT26 neoepitopes with the ability to bind MHC-I and MHC-II, TCR, and induce IFN-α production were selected. To increase their immunogenicity, the gp70 and PADRE epitopes were added. The order of the neoepitopes was determined through 3D structure analysis using ProSA, Verify 3D, ERRAT, and Ramachandran servers. The stable peptide-protein docking between the selected epitopes and MHC alleles strengthen our prediction. The CT26 polytope vaccine sequence was fused to the C-terminal of cytolysin A (ClyA) anchor protein and rOMVs were isolated from endotoxin-free ClearColi™ strain. The results of the C-ImmSim server showed that the ClyA-CT26 polytope vaccine could induce T and B cells immunity.The ClyA-CT26 polytope was characterized as a soluble, stable, immunogen, and non-allergen vaccine and optimized for expression in ClearColi™ 24 h after induction with 1 mM IPTG at 25 °C. Western blot analysis confirmed the expression of ClyA-CT26 polytope by ClearColi™ and also on ClearColi™-derived rOMVs. In conclusion, we found that ClearColi™-derived rOMVs with CT26 polytope can deliver CRC neoantigens and induce antitumor immunity, but in vivo immunological studies are needed to confirm vaccine efficacy.

RESUMEN

INTRODUCTION: This immunoinformatic study identified potential epitopes from the envelopment polyprotein (Gn/Gc) of Rift Valley fever virus (RVFV), a pathogenic virus causing severe fever in humans and livestock. Effective vaccination is crucial for controlling RVFV outbreaks. The identification of suitable epitopes is crucial for the development of safe and effective vaccines. METHODOLOGY: Protein sequences were obtained from the UniProt database, and evaluated through VaxiJen v2.0 to predict the B and T-cell epitopes within the RVFV glycoprotein. Gn/Gc protein sequences were analyzed with bioinformatics tools and algorithms. The predicted T-cell and B-cell epitopes were evaluated for antigenicity, allergenicity, and toxicity by the VaxiJen v2.0 system, AllerTop v2.0, and ToxinPred server, respectively. RESULTS: We employed computational methods to screen the RVFV envelopment polyprotein encompassing N-terminal and C-terminal glycoprotein segments, to discover antigenic T- and B-cell epitopes. Our analysis unveiled multiple potential epitopes within the RVFV glycoprotein, specifically within the Gn/Gc protein sequences. Subsequently, we selected eleven cytotoxic T-lymphocytes (CTL) and four helper T-lymphocytes (HTL) for population coverage analysis, which collectively extended to cover 97.04% of the world's population, representing diverse ethnicities and regions. Notably, the CTL epitope VQADLTLMF exhibited binding affinity to numerous human leukocyte antigen (HLA) alleles. The identification of glycoprotein (Gn/Gc) epitopes through this immunoinformatic study bears significant implications for advancing the development of an effective RVFV vaccine. CONCLUSIONS: These findings provide valuable insights into the immunological aspects of the disease and may contribute towards the development of broad-spectrum antiviral therapies targeting other RNA viruses with similar polymerase enzymes.

Asunto(s)

RESUMEN

Epstein-Barr Virus (EBV), structurally similar to other herpes viruses, possess significant global health challenges as it causes infectious mononucleosis and is also associated with various cancers. Due to this widespread impact, an effective messenger RNA (mRNA) vaccine is paramount to help curb its spread, further underscoring the need for its development. This study, following an immunoinformatic approach, aimed to design a comprehensive mRNA vaccine against the EBV by selecting antigenic proteins, predicting Linear B-cell epitopes, cytotoxic T-cell lymphocyte (CTL) and helper T-cell lymphocyte (HTL) epitopes, and assessing vaccine characteristics. Seventy-nine EBV isolates from diverse geographical regions were examined. Additionally, the vaccine construct's physicochemical properties, transmembrane domains, solubility, and secondary structures were analysed. Molecular docking was conducted with Toll-Like Receptor 5 (TLR-5). Population coverage was assessed for selected major histocompatibility complex (MHC) alleles, and immune response was simulated. The result of this study highlighted a vaccine construct with high antigenicity, non-toxicity, and non-allergenicity and possessed favourable physicochemical properties. The vaccine's 3D structure is native-like and strongly binds with TLR-5, indicating a solid affinity with TLR-5. The selected MHC alleles provided broad universal population coverage of 89.1%, and the immune simulations suggested a robust and wide-ranging immunogenic response, activating critical immune cells, antibodies, and cytokines. These findings provide a solid foundation for further development and testing of the EBV candidate vaccine, offering potential solutions for combating EBV infections.

RESUMEN

Spirocerca lupi is a parasitic nematode affecting predominantly domestic dogs. It causes spirocercosis, a disease that is often fatal. The assembled draft genome of S. lupi consists of 13,627 predicted protein-coding genes and is approximately 150 Mb in length. Several known anthelmintic gene targets such as for ß-Tubulin, glutamate, and GABA receptors as well as known vaccine gene targets such as cysteine protease inhibitor and cytokines were identified in S. lupi by comparing orthologs of C. elegans anthelmintic gene targets as well as orthologs to known vaccine candidates. New anthelmintic targets were predicted through an inclusion-exclusion strategy and new vaccine targets were predicted through an immunoinformatics approach. New anthelminthic targets include DNA-directed RNA polymerases, chitin synthase, polymerases, and other enzymes. New vaccine targets include cuticle collagens. These gene targets provide a starting platform for new drug identification and vaccine design.

Asunto(s)

RESUMEN

Background The pathogen Orientia tsutsugamushi, which causes scrub typhus, is rapidly spreading throughout the tropics. As a measure to improve public health, the development of a vaccine for human use is essential. Scrub typhus is listed as one of the underdiagnosed and underreported febrile infections. This vector-borne zoonotic infection appears as eschar on the patient's skin. Methods Immunoinformatics was employed to predict the multi-epitope subunit vaccine that will activate both B and T cells. The final vaccine includes lipoprotein LprA as an adjuvant at the N-terminus along with B-cell, helper T lymphocyte (HTL), and cytotoxic T lymphocyte (CTL)-binding epitopes to boost immunogenicity. Assessing the vaccine's physiochemistry demonstrates that it is both antigenic and non-allergic. The vaccine structure was developed, enhanced, confirmed, and disulfide-engineered to provide the best possible model. Using molecular docking, the interaction of the produced vaccine with toll-like receptor 2 (TLR2) was analyzed, and the vaccine-receptor complex was stabilized by molecular dynamics (MD) simulation. According to in silico cloning, Escherichia coli can efficiently produce the recommended vaccine. Additionally, the efficacy of the in silico-developed vaccine must be evaluated in an in vitro and in vivo experiment. Results The developed vaccine successfully stimulates cellular and humoral immune responses. The vaccine, which has three B-cell epitopes, three HCL epitopes, and nine CTL epitopes, can bind firmly to immunological receptors. Dynamic investigations of the vaccine-receptor complex show a strong interaction and stable conformation. Conclusion In this study, the vaccine candidate demonstrated strong antigenicity, stability, and solubility while also being non-allergenic to host cells. The vaccine candidate's stability with the TLR2 immune receptor is established by binding studies, and in silico cloning verifies efficient and stable expression in the bacterial system.

RESUMEN

Despite advancements in vaccinology, there is currently no effective anti-HIV vaccine. One strategy under investigation is based on the identification of epitopes recognized by broadly neutralizing antibodies to include in vaccine preparation. Taking into account the benefits of anti-idiotype molecules and the diverse biological attributes of different antibody formats, our aim was to identify the most immunogenic antibody format. This format could serve as a foundational element for the development of an oligo-polyclonal anti-idiotype vaccine against HIV-1. For our investigation, we anchored our study on an established b12 anti-idiotype, referred to as P1, and proposed four distinct formats: two single chains and two minibodies, both in two different orientations. For a deeper characterization of these molecules, we used immunoinformatic tools and tested them on rabbits. Our studies have revealed that a particular minibody conformation, MbVHVL, emerges as the most promising candidate. It demonstrates a significant binding affinity with b12 and elicits a humoral anti-HIV-1 response in rabbits similar to the Fab format. This study marks the first instance where the minibody format has been shown to provoke a humoral response against a pathogen. Furthermore, this format presents biological advantages over the Fab format, including bivalency and being encoded by a monocistronic gene, making it better suited for the development of RNA-based vaccines.

Asunto(s)

RESUMEN

Diagnosing canine visceral leishmaniasis (CVL) in Brazil faces challenges due to the limitations regarding the sensitivity and specificity of the current diagnostic protocol. Therefore, it is urgent to map new antigens or enhance the existing ones for future diagnostic techniques. Immunoinformatic tools are promising in the identification of new potential epitopes or antigen candidates. In this study, we evaluated peptides selected by epitope prediction for CVL serodiagnosis in ELISA assays. Ten B-cell epitopes were immunogenic in silico, but two peptides (peptides No. 45 and No. 48) showed the best performance in vitro. The selected peptides, both individually and in combination, were highly diagnostically accurate, with sensitivities ranging from 86.4% to 100% and with a specificity of approximately 90%. We observed that the combination of peptides showed better performance when compared to peptide alone, by detecting all asymptomatic dogs, showing lower cross-reactivity in sera from dogs with other canine infections, and did not detect vaccinated animals. Moreover, our data indicate the potential use of immunoinformatic tools associated with ELISA assays for the selection and evaluation of potential new targets, such as peptides, applied to the diagnosis of CVL.

RESUMEN

Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( ß -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.

Asunto(s)

RESUMEN

Nonenveloped virus-like particles (VLPs) are self-assembled oligomeric structures composed of one or more proteins that originate from diverse viruses. Because these VLPs have similar antigenicity to the parental virus, they are successfully used as vaccines against cognate virus infection. Furthermore, after foreign antigenic sequences are inserted in their protein components (chimVLPs), some VLPs are also amenable to producing vaccines against pathogens other than the virus it originates from (these VLPs are named platform or epitope carrier). Designing chimVLP vaccines is challenging because the immunogenic response must be oriented against a given antigen without altering stimulant properties inherent to the VLP. An important step in this process is choosing the location of the sequence modifications because this must be performed without compromising the assembly and stability of the original VLP. Currently, many immunogenic data and computational tools can help guide the design of chimVLPs, thus reducing experimental costs and work. In this study, we analyze the structure of a novel VLP that originate from an insect virus and describe the putative regions of its three structural proteins amenable to insertion. For this purpose, we employed molecular dynamics (MD) simulations to assess chimVLP stability by comparing mutated and wild-type (WT) VLP protein trajectories. We applied this procedure to design a chimVLP that can serve as a prophylactic vaccine against the SARS-CoV-2 virus. The methodology described in this work is generally applicable for VLP-based vaccine development.

Asunto(s)

RESUMEN

Streptococcus suis (S. suis) is a zoonotic pathogen with multiple serotypes, and thus, multivalent vaccines generating cross-protection against S. suis infections are urgently needed to improve animal welfare and reduce antibiotic abuse. In this study, we established a systematic and comprehensive epitope prediction pipeline based on immunoinformatics. Ten candidate epitopes were ultimately selected for building the multi-epitope vaccine (MVSS) against S. suis infections. The ten epitopes of MVSS were all derived from highly conserved, immunogenic, and virulence-associated surface proteins in S. suis. In silico analyses revealed that MVSS was structurally stable and affixed with immune receptors, indicating that it would likely trigger strong immunological reactions in the host. Furthermore, mice models demonstrated that MVSS elicited high titer antibodies and diminished damages in S. suis serotype 2 and Chz infection, significantly reduced sequelae, induced cytokine transcription, and decreased organ bacterial burdens after triple vaccination. Meanwhile, anti-rMVSS serum inhibited five important S. suis serotypes in vitro, exerted beneficial protective effects against S. suis infections and significantly reduced histopathological damage in mice. Given the above, it is possible to develop MVSS as a universal subunit vaccine against multiple serotypes of S. suis infections.

RESUMEN

The Monkeypox virus, an Orthopoxvirus with zoonotic origins, has been responsible for a growing number of human infections reminiscent of smallpox since May 2022, as reported by the World Health Organization. As of now, there are no established medical treatments for managing Monkeypox infections. In this study, we used machine learning to select conserved epitopes. Proteins were determined using Reverse Vaccinology and Gene Ontology subcellular localization, and their epitopes were predicted. NextClade was used to calculate the number of mutations in each amino acid position using 2433 Monkeypox sequences. The Unsupervised Nearest Neighbor machine learning algorithm and ideal matrix [0 0] were used to calculate the conservancy score of epitopes. Six proteins were determined for epitope prediction. Finally, 47 MHC-I epitopes, 5 MHC-II epitopes, and 10 Linear B cell epitopes were discovered. Our method can select epitopes for vaccine design to prevent viruses with accelerated evolution and high mutation rate.

RESUMEN

Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against Histoplasma, with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine's efficacy in in vivo models.

RESUMEN

@#Rhipicephalus microplus, known as the hard tick, is a vector for the parasites Babesia spp. and Anaplasma marginale, both of which can cause significant financial losses to the livestock industry. There is currently no effective vaccine for R. microplus tick infestations, despite the identification of numerous prospective tick vaccine candidates. As a result, the current research set out to develop an immunoinformatics-based strategy using existing methods for designing a multi-epitope based vaccination that is not only effective but also safe and capable of eliciting cellular and humoral immune responses. First, R. microplus proteins Bm86, Subolesin, and Bm95 were used to anticipate and link B and T-cell epitopes (HTL and CTL) to one another. Antigenicity testing, allergenicity assessment, and toxicity screening were just a few of the many immunoinformatics techniques used to identify potent epitopes. Multi-epitope vaccine design was chosen based on the antigenic score 0.935 that is promising vaccine candidate. Molecular docking was used to determine the nature of the interaction between TLR2 and the vaccine construct. Finally, molecular dynamic simulation was used to assess the stability and compactness of the resulting vaccination based on docking scores. The developed vaccine was shown to be stable, have immunogenic qualities, be soluble, and to have high expression by in silico cloning. These findings suggest that experimental investigation of the multi-epitope based vaccine designed in the current study will produce achievable vaccine candidates against R. microplus ticks, enabling more effective control of infestations.

Asunto(s)

RESUMEN

Leptospira, the pathogenic helical spirochetes that cause leptospirosis, is an emerging zoonotic disease with effective dissemination tactics in the host and can infect humans and animals with moderate or severe illnesses. Thus, peptide-based vaccines may be the most effective strategy to manage the immune response against Leptospira to close these gaps. In the current investigation, highly immunogenic proteins from the proteome of Leptospira interorgan serogroup Icterohaemorrhagie serovar Lai strain 56601 were identified using immunoinformatic methods. It was discovered that the conserved and most immunogenic outer membrane Lepin protein was both antigenic and non-allergenic by testing 15 linear B-cells and the ten best T-cell (Helper-lymphocyte (HTL) with the most significant number of HLA-DR binding alleles and the eight cytotoxic T lymphocyte (CTL)) epitopes. Furthermore, a 3D structural model of CTL epitopes was created using the Pep-Fold3 platform. Using the Autodock 4.2 docking server, research was conducted to determine how well the top-ranked CTL peptide models attach to HLA-A*0201 (PDB ID: 4U6Y). With HLA-A*0201, the epitope SSGTGNLHV binds with a binding energy of -1.29 kcal/mol. Utilizing molecular dynamics modeling, the projected epitope-allele docked complex structure was optimized, and the stability of the complex system was assessed. Therefore, this epitope can trigger an immunological response and produce effective Leptospira vaccine candidates. Overall, this study offers a unique vaccination candidate and may encourage additional research into leptospirosis vaccines.Communicated by Ramaswamy H. Sarma.

RESUMEN

For protection against Pseudomonas aeruginosa strains, a number of vaccine candidates have been introduced thus far. However, despite significant attempts in recent years, there are currently no effective immunogenic Bacteria components against this pathogen on the market. P. aeruginosa encoding a number of different virulence characteristics, as well as the rapid growth in multiple drug-resistant forms, has raised numerous health issues throughout the world. This pathogen expresses three different subtypes of T4P, including IVa, IVb, and Tad which are involved in various cellular processes. Highly virulent strains of P. aeruginosa can encode well-conserved PAPI-1 associated PilS2 pilus. Designing an efficient pili-based immunotherapy approach targeting P. aeruginosa pilus has remained controversial due to the variability heterogeneousness and hidden well-preserved binding site of T4aP and no approved human study is commercially based on IVa pilin. In this investigation, for the first time, through analytical immunoinformatics, we designed an effective chimeric PilS2 immunogen against numerous clinically important P. aeruginosa strains. Through active immunization against the extremely conserved region of the chimeric PilS2 pilin, we showed that PilS2 chimeric pilin whether administered alone or formulated with alum as an adjuvant could substantially stimulate humoral immunological responses in BALB/c mice. Based on these findings, we conclude that PilS2 pilin is therapeutically effective against a variety of highly virulent strains of P. aeruginosa and can act as a new immunogen for more research towards the creation of efficient immunotherapy techniques against the P. aeruginosa as a dexterous pathogen.

Asunto(s)

RESUMEN

Introduction: The Bacillus Calmette-Guérin (BCG) vaccine, currently used against tuberculosis (TB), exhibits inconsistent efficacy, highlighting the need for more potent TB vaccines. Materials and methods: In this study, we employed reverse vaccinology techniques to develop a promising multi-epitope vaccine (MEV) candidate, called PP13138R, for TB prevention. PP13138R comprises 34 epitopes, including B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes. Using bioinformatics and immunoinformatics tools, we assessed the physicochemical properties, structural features, and immunological characteristics of PP13138R. Results: The vaccine candidate demonstrated excellent antigenicity, immunogenicity, and solubility without any signs of toxicity or sensitization. In silico analyses revealed that PP13138R interacts strongly with Toll-like receptor 2 and 4, stimulating innate and adaptive immune cells to produce abundant antigen-specific antibodies and cytokines. In vitro experiments further supported the efficacy of PP13138R by significantly increasing the population of IFN-γ+ T lymphocytes and the production of IFN-γ, TNF-α, IL-6, and IL-10 cytokines in active tuberculosis patients, latent tuberculosis infection individuals, and healthy controls, revealing the immunological characteristics and compare the immune responses elicited by the PP13138R vaccine across different stages of Mycobacterium tuberculosis infection. Conclusion: These findings highlight the potential of PP13138R as a promising MEV candidate, characterized by favorable antigenicity, immunogenicity, and solubility, without any toxicity or sensitization.

Asunto(s)