Subject(s)
Immunity, Mucosal , Immunoglobulin A , Humans , Immunoglobulin A/immunology , Vaccinology/methods , Vaccines/immunology , Animals , VaccinationABSTRACT
Pancreatic ductal adenocarcinoma is the most prevalent pancreatic cancer, which is considered a significant global health concern. Chemotherapy and surgery are the mainstays of current pancreatic cancer treatments; however, a few cases are suitable for surgery, and most of the cases will experience recurrent episodes. Compared to DNA or peptide vaccines, mRNA vaccines for pancreatic cancer have more promise because of their delivery, enhanced immune responses, and lower proneness to mutation. We constructed an mRNA vaccine by analyzing S100 family proteins, which are all major activators of receptors for advanced glycation end products. We applied immunoinformatic approaches, including physicochemical properties analysis, structural prediction and validation, molecular docking study, in silico cloning, and immune simulations. The designed mRNA vaccine was estimated to have a molecular weight of 165023.50 Da and was highly soluble (grand average of hydropathicity of -0.440). In the structural assessment, the vaccine seemed to be a well-stable and functioning protein (Z score of -8.94). Also, the docking analysis suggested that the vaccine had a high affinity for TLR-2 and TLR-4 receptors. Additionally, the molecular mechanics with generalized Born and surface area solvation analysis of the "Vaccine-TLR-2" (-141.07 kcal/mol) and "Vaccine-TLR-4" (-271.72 kcal/mol) complexes also suggests a strong binding affinity for the receptors. Codon optimization also provided a high expression level with a GC content of 47.04% and a codon adaptation index score 1.0. The appearance of memory B-cells and T-cells was also observed over a while, with an increased level of helper T-cells and immunoglobulins (IgM and IgG). Moreover, the minimum free energy of the mRNA vaccine was predicted at -1760.00 kcal/mol, indicating the stability of the vaccine following its entry, transcription, and expression. This hypothetical vaccine offers a groundbreaking tool for future research and therapeutic development of pancreatic cancer.
Subject(s)
Cancer Vaccines , Molecular Docking Simulation , Pancreatic Neoplasms , Pancreatic Neoplasms/immunology , Humans , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , mRNA Vaccines/immunology , Computational Biology/methods , Toll-Like Receptor 4/immunology , Toll-Like Receptor 4/metabolism , Vaccinology/methods , Toll-Like Receptor 2/immunology , Computer Simulation , RNA, Messenger/genetics , RNA, Messenger/immunology , ImmunoinformaticsABSTRACT
Rotavirus, a primary contributor to severe cases of infantile gastroenteritis on a global scale, results in significant morbidity and mortality in the under-five population, particularly in middle to low-income countries, including India. WHO-approved live-attenuated vaccines are linked to a heightened susceptibility to intussusception and exhibit low efficacy, primarily attributed to the high genetic diversity of rotavirus, varying over time and across different geographic regions. Herein, molecular data on Indian rotavirus A (RVA) has been reviewed through phylogenetic analysis, revealing G1P[8] to be the prevalent strain of RVA in India. The conserved capsid protein sequences of VP7, VP4 and VP6 were used to examine helper T lymphocyte, cytotoxic T lymphocyte and linear B-cell epitopes. Twenty epitopes were identified after evaluation of factors such as antigenicity, non-allergenicity, non-toxicity, and stability. These epitopes were then interconnected using suitable linkers and an N-terminal beta defensin adjuvant. The in silico designed vaccine exhibited structural stability and interactions with integrins (αvß3 and αIIbß3) and toll-like receptors (TLR2 and TLR4) indicated by docking and normal mode analyses. The immune simulation profile of the designed RVA multiepitope vaccine exhibited its potential to trigger humoral as well as cell-mediated immunity, indicating that it is a promising immunogen. These computational findings indicate potential efficacy of the designed vaccine against rotavirus infection.
Subject(s)
Antigens, Viral , Capsid Proteins , Epitopes, T-Lymphocyte , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Rotavirus/immunology , Rotavirus/genetics , Rotavirus Vaccines/immunology , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/genetics , Rotavirus Infections/prevention & control , Rotavirus Infections/immunology , Capsid Proteins/immunology , Capsid Proteins/genetics , Capsid Proteins/chemistry , Antigens, Viral/immunology , Antigens, Viral/genetics , Humans , India , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Vaccinology/methods , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/genetics , Phylogeny , Molecular Docking Simulation , Epitopes/immunology , Epitopes/genetics , Vaccine DevelopmentABSTRACT
Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage.
Subject(s)
Orthohantavirus , Viral Vaccines , Orthohantavirus/immunology , Viral Vaccines/immunology , Humans , Vaccinology/methods , Molecular Docking Simulation , Computer Simulation , Epitopes/immunology , Epitopes/chemistry , Models, Molecular , Hantavirus Infections/prevention & control , Hantavirus Infections/immunologyABSTRACT
BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen. METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity. OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used. RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1). CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.
Subject(s)
Pneumocystis carinii , Pneumonia, Pneumocystis , Proteomics , Vaccinology , mRNA Vaccines , Proteomics/methods , Pneumocystis carinii/immunology , Pneumocystis carinii/genetics , Humans , Vaccinology/methods , mRNA Vaccines/immunology , Pneumonia, Pneumocystis/prevention & control , Pneumonia, Pneumocystis/immunology , Pneumonia, Pneumocystis/microbiology , Fungal Vaccines/immunology , Fungal Proteins/immunology , Fungal Proteins/genetics , Proteome/immunology , RNA, Messenger/genetics , RNA, Messenger/immunology , Vaccine Development/methods , Vaccines, Synthetic/immunologyABSTRACT
OBJECTIVES: The pathogenic microorganisms that cause intestinal diseases can significantly jeopardize people's health. Currently, there are no authorized treatments or vaccinations available to combat the germs responsible for intestinal disease. METHODS: Using immunoinformatics, we developed a potent multi-epitope Combination (combo) vaccine versus Salmonella and enterohemorrhagic E. coli. The B and T cell epitopes were identified by performing a conservancy assessment, population coverage analysis, physicochemical attributes assessment, and secondary and tertiary structure assessment of the chosen antigenic polypeptide. The selection process for vaccine development included using several bioinformatics tools and approaches to finally choose two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes. RESULTS: The vaccine had strong immunogenicity, cytokine production, immunological properties, non-toxicity, non-allergenicity, stability, and potential efficacy against infections. Disulfide bonding, codon modification, and computational cloning were also used to enhance the stability and efficacy of expression in the host E. coli. The vaccine's structure has a strong affinity for the TLR4 ligand and is very durable, as shown by molecular docking and molecular modeling. The results of the immunological simulation demonstrated that both B and T cells had a heightened response to the vaccination component. CONCLUSIONS: The comprehensive in silico analysis reveals that the proposed vaccine will likely elicit a robust immune response against pathogenic bacteria that cause intestinal diseases. Therefore, it is a promising option for further experimental testing.
Subject(s)
Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Vaccinology , Humans , Epitopes, T-Lymphocyte/immunology , Vaccinology/methods , Epitopes, B-Lymphocyte/immunology , Vaccines, Combined/immunology , Genomics/methods , Enterohemorrhagic Escherichia coli/immunology , Salmonella/immunology , Animals , Computational Biology/methods , Molecular Docking Simulation , Escherichia coli Vaccines/immunology , Escherichia coli Infections/prevention & control , Escherichia coli Infections/immunology , Salmonella Infections/immunology , Salmonella Infections/prevention & control , Antigens, Bacterial/immunology , Vaccine Development/methods , Bacterial Vaccines/immunologyABSTRACT
Neisseria meningitidis, commonly known as the meningococcus, leads to substantial illness and death among children and young adults globally, revealing as either epidemic or sporadic meningitis and/or septicemia. In this study, we have designed a novel peptide-based chimeric vaccine candidate against the N. meningitidis strain 331,401 serogroup X. Through rigorous analysis of subtractive genomics, two essential cytoplasmic proteins, namely UPI000012E8E0(UDP-3-O-acyl-GlcNAc deacetylase) and UPI0000ECF4A9(UDP-N-acetylglucosamine acyltransferase) emerged as potential drug targets. Additionally, using reverse vaccinology, the outer membrane protein UPI0001F4D537 (Membrane fusion protein MtrC) identified by subcellular localization and recognized for its known indispensable role in bacterial survival was identified as a novel chimeric vaccine target. Following a careful comparison of MHC-I, MHC-II, T-cell, and B-cell epitopes, three epitopes derived from UPI0001F4D537 were linked with three types of linkers-GGGS, EAAAK, and the essential PADRE-for vaccine construction. This resulted in eight distinct vaccine models (V1-V8). Among them V1 model was selected as the final vaccine construct. It exhibits exceptional immunogenicity, safety, and enhanced antigenicity, with 97.7 % of its residues in the Ramachandran plot's most favored region. Subsequently, the vaccine structure was docked with the TLR4/MD2 complex and six different HLA allele receptors using the HADDOCK server. The docking resulted in the lowest HADDOCK score of 39.3 ± 9.0 for TLR/MD2. Immune stimulation showed a strong immune response, including antibodies creation and the activation of B-cells, T Cytotoxic cells, T Helper cells, Natural Killer cells, and interleukins. Furthermore, the vaccine construct was successfully expressed in the Escherichia coli system by reverse transcription, optimization, and ligation in the pET-28a (+) vector for the expression study. The current study proposes V1 construct has the potential to elicit both cellular and humoral responses, crucial for the developing an epitope-based vaccine against N. meningitidis strain 331,401 serogroup X.
Subject(s)
Meningococcal Vaccines , Neisseria meningitidis , Neisseria meningitidis/immunology , Neisseria meningitidis/genetics , Humans , Meningococcal Vaccines/immunology , Vaccinology/methods , Genomics , Computer Simulation , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/geneticsABSTRACT
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.
Subject(s)
Epitopes, T-Lymphocyte , Yellow Fever Vaccine , Yellow Fever , Yellow fever virus , Yellow Fever Vaccine/immunology , Yellow fever virus/immunology , Yellow fever virus/genetics , Humans , Yellow Fever/prevention & control , Yellow Fever/immunology , Epitopes, T-Lymphocyte/immunology , Epitopes, B-Lymphocyte/immunology , Vaccinology/methods , Models, Molecular , Vaccine Development , Molecular Dynamics Simulation , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
Reverse vaccinology (RV) is a significant step in sensible vaccine design. In recent years, many machine learning (ML) methods have been used to improve RV prediction accuracy. However, there are still issues with prediction accuracy and programme accessibility in ML-based RV. This paper presents a supervised ML-based method to classify bacterial protective antigens (BPAgs) and identify the model(s) that consistently perform well for the training dataset. Six ML classifiers are used for testing with physiochemical features extracted from a comprehensive training dataset. Selecting the best performing model from different performance metrics (accuracy, precision, recall, F1-score, and AUC-ROC) has not been easy, because all the metrics has the same importance to predict BPAgs. To fix this issue, we propose a soft and hard ranking model based on multi-criteria decision-making (MCDM) approach for selecting the best performing ML method that classifies BPAgs. First, our proposed model uses homologous proteins (positive and negative samples) from Protegen and Uniprot databases. Second, we applied four strategies of Synthetic Minority Oversampling Technique and Edited Nearest Neighbour (SMOTE-ENN) to handle the data imbalance problem and train the model using ML methods. Third, we consider MCDM-based technique for order preference by similarity to the ideal solution (TOPSIS) method integrated with soft and hard ranking model. The entropy is used to obtain weighted evaluation criteria for ranking the models. Our experimental evaluations show that the proposed method with best performing models (Random Forest and Extreme Gradient Boosting) outperforms compared to existing open-source RV methods using benchmark datasets.
Subject(s)
Antigens, Bacterial , Vaccinology , Antigens, Bacterial/immunology , Vaccinology/methods , Machine Learning , Humans , Bacterial Vaccines/immunologyABSTRACT
INTRODUCTION: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges. AREAS COVERED: Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos' optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors in zebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunological reagents for challenge studies. 4) Systems vaccinology: Due to the availability of a well-referenced zebrafish genome, transcriptome, proteome, and epigenome, this model offers potential here. EXPERT OPINION: It remains unproven whether zebrafishes can be employed for testing and developing human vaccines. We are still at the hypothesis-generating stage, although it is possible to begin outlining experiments for this purpose. Through transgenic manipulation, zebrafish models could offer new paths for shaping animal models and systems vaccinology.
Subject(s)
Adaptive Immunity , Adjuvants, Immunologic , Immunity, Innate , Models, Animal , Vaccine Development , Vaccines , Zebrafish , Zebrafish/immunology , Animals , Adjuvants, Immunologic/administration & dosage , Humans , Vaccines/immunology , Vaccines/administration & dosage , Vaccinology/methodsABSTRACT
Despite the efforts of global programme to eliminate lymphatic filariasis (GPELF), the threat of lymphatic filariasis (LF) still looms over humanity in terms of long-term disabilities, and morbidities across the globe. In light of this situation, investigators have chosen to focus on the development of immunotherapeutics targeting the physiologically important filarial-specific proteins. Glutaredoxin (16.43 kDa) plays a pivotal role in filarial redox biology, serving as a vital contributor. In the context of the intra-host survival of filarial parasites, this antioxidant helps in mitigating the oxidative stress imposed by the host immune system. Given its significant contribution, the development of a vaccine targeting glutaredoxin holds promise as a new avenue for achieving a filaria-free world. Herein, multi-epitope-based vaccine was designed using advanced immunoinformatics approach. Initially, 4B-cell epitopes and 6 T-cell epitopes (4 MHC I and 2 MHC II) were identified from the 146 amino acid long sequence of glutaredoxin of the human filarid, Wuchereria bancrofti. Subsequent clustering of these epitopes with linker peptides finalized the vaccine structure. To boost TLR-mediated innate immunity, TLR-specific adjuvants were incorporated into the designed vaccine. After that, experimental analyses confirm the designed vaccine, Vac4 as anefficient ligand of human TLR5 to elicit protective innate immunity against filarial glutaredoxin. Immune simulation further demonstrated abundant levels of IgG and IgM as crucial contributors in triggering vaccine-induced adaptive responses in the recipients. Hence, to facilitate the validation of immunogenicity of the designed vaccine, Vac4 was cloned in silico in pET28a(+) expression vector for recombinant production. Taken together, our findings suggest that vaccine-mediated targeting of filarial glutaredoxin could be a future option for intervening LF on a global scale.
Subject(s)
Elephantiasis, Filarial , Glutaredoxins , Wuchereria bancrofti , Glutaredoxins/immunology , Glutaredoxins/metabolism , Animals , Elephantiasis, Filarial/prevention & control , Elephantiasis, Filarial/immunology , Humans , Wuchereria bancrofti/immunology , Epitopes, T-Lymphocyte/immunology , Vaccinology/methods , Epitopes, B-Lymphocyte/immunology , Vaccines, Subunit/immunology , Mice , Antigens, Helminth/immunology , Female , Mice, Inbred BALB CABSTRACT
Vaccines have significantly reduced the impact of numerous deadly viral infections. However, there is an increasing need to expedite vaccine development in light of the recurrent pandemics and epidemics. Also, identifying vaccines against certain viruses is challenging due to various factors, notably the inability to culture certain viruses in cell cultures and the wide-ranging diversity of MHC profiles in humans. Fortunately, reverse vaccinology (RV) efficiently overcomes these limitations and has simplified the identification of epitopes from antigenic proteins across the entire proteome, streamlining the vaccine development process. Furthermore, it enables the creation of multiepitope vaccines that can effectively account for the variations in MHC profiles within the human population. The RV approach offers numerous advantages in developing precise and effective vaccines against viral pathogens, including extensive proteome coverage, accurate epitope identification, cross-protection capabilities, and MHC compatibility. With the introduction of RV, there is a growing emphasis among researchers on creating multiepitope-based vaccines aiming to stimulate the host's immune responses against multiple serotypes, as opposed to single-component monovalent alternatives. Regardless of how promising the RV-based vaccine candidates may appear, they must undergo experimental validation to probe their protection efficacy for real-world applications. The time, effort, and resources allocated to the laborious epitope identification process can now be redirected toward validating vaccine candidates identified through the RV approach. However, to overcome failures in the RV-based approach, efforts must be made to incorporate immunological principles and consider targeting the epitope regions involved in disease pathogenesis, immune responses, and neutralizing antibody maturation. Integrating multi-omics and incorporating artificial intelligence and machine learning-based tools and techniques in RV would increase the chances of developing an effective vaccine. This review thoroughly explains the RV approach, ideal RV-based vaccine construct components, RV-based vaccines designed to combat viral pathogens, its challenges, and future perspectives.
Subject(s)
Artificial Intelligence , Vaccines , Humans , Proteome , Vaccinology/methods , Epitopes , Computational Biology/methods , Vaccines, Subunit , Epitopes, T-Lymphocyte , Molecular Docking Simulation , Epitopes, B-LymphocyteABSTRACT
Introduction: The COVID-19 pandemic had a profound impact on vaccines' Research and Development, on vaccines' market, and on immunization programmes and policies. The need to promptly respond to the health emergency boostered resources' al-location and innovation, while new technologies were made available. Regulatory procedures were revised and expedited, and global production and distribution capacities significantly increased. Aim of this review is to outline the trajectory of research in vaccinology and vaccines' pipeline, highlighting major challenges and opportunities, and projecting future perspectives in vaccine preventables diseases' prevention and control. Study Design: Narrative review. Methods: We comprehensively consulted key biomedical databases including "Medline" and "Embase", preprint platforms, including"MedRxiv" and "BioRxiv", clinical trial registries, selected grey literature sources and scientific reports. Further data and insights were collected from experts in the field. We first reflect on the impact that the COVID-19 had on vaccines' Research and Development, regulatory frameworks, and market, we then present updated figures of vaccines pipeline, by different technologies, comparatively highlighting advantages and disadvantages. We conclude summarizing future perspectives in vaccines' development and immunizations strategies, outlining key challenges, knowledge gaps and opportunities for prevention strategies. Results: COVID-19 vaccines' development has been largely supported by public funding. New technologies and expetited autho-rization and distribution processes allowed to control the pandemic, leading vaccines' market to grow exponentially. In the post-pandemic era investments in prevention are projected to decrease but advancements in technology offer great potential to future immunization strategies. As of 2023, the vaccine pipeline include almost 1,000 candidates, at different Research and Development phase, including innovative recombinant protein vaccines, nucleic acid vaccines and viral vector vaccines. Vaccines' technology platforms development varies by disease. Overall, vaccinology is progressing towards increasingly safe and effective products that are easily manufacturable and swiftly convertible. Conclusions: Vaccine research is rapidly evolving, emerging technologies and new immunization models offer public health new tools and large potential to fight vaccines preventables diseases, with promising new platforms and broadened target populations. Real-life data analysis and operational research is needed to evaluate how such potential is exploited in public health practice to improve population health.
Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccine Development , Humans , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , Pandemics/prevention & control , Forecasting , Biomedical Research/trends , Vaccinology/trends , Vaccinology/methods , Immunization Programs/trends , Drug Development/trendsABSTRACT
Systems vaccinology studies have identified factors affecting individual vaccine responses, but comparing these findings is challenging due to varying study designs. To address this lack of reproducibility, we established a community resource for comparing Bordetella pertussis booster responses and to host annual contests for predicting patients' vaccination outcomes. We report here on our experiences with the "dry-run" prediction contest. We found that, among 20+ models adopted from the literature, the most successful model predicting vaccination outcome was based on age alone. This confirms our concerns about the reproducibility of conclusions between different vaccinology studies. Further, we found that, for newly trained models, handling of baseline information on the target variables was crucial. Overall, multiple co-inertia analysis gave the best results of the tested modeling approaches. Our goal is to engage community in these prediction challenges by making data and models available and opening a public contest in August 2024.
Subject(s)
Multiomics , Vaccines , Humans , Vaccinology/methods , Reproducibility of Results , Computer SimulationABSTRACT
Viruses transmitted by arthropods, such as Dengue, Zika, and Chikungunya, represent substantial worldwide health threats, particularly in countries like India. The lack of approved vaccines and effective antiviral therapies calls for developing innovative strategies to tackle these arboviruses. In this study, we employed immunoinformatics methodologies, incorporating reverse vaccinology, to design a multivalent vaccine targeting the predominant arboviruses. Epitopes of B and T cells were recognized within the non-structural proteins of Dengue, Zika, and Chikungunya viruses. The predicted epitopes were enhanced with adjuvants ß-defensin and RS-09 to boost the vaccine's immunogenicity. Sixteen distinct vaccine candidates were constructed, each incorporating epitopes from all three viruses. FUVAC-11 emerged as the most promising vaccine candidate through molecular docking and molecular dynamics simulations, demonstrating favorable binding interactions and stability. Its effectiveness was further evaluated using computational immunological studies confirming strong immune responses. The in silico cloning performed using the pET-28a(+) plasmid facilitates the future experimental implementation of this vaccine candidate, paving the way for potential advancements in combating these significant arboviral threats. However, further in vitro and in vivo studies are warranted to confirm the results obtained in this computational study, which highlights the effectiveness of immunoinformatics and reverse vaccinology in creating vaccines against major Arboviruses, offering a promising model for developing vaccines for other vector-borne diseases and enhancing global health security.