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2.
Sci Rep ; 14(1): 10842, 2024 05 12.
Article in English | MEDLINE | ID: mdl-38735993

ABSTRACT

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/immunology
3.
BMC Vet Res ; 20(1): 144, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38641595

ABSTRACT

BACKGROUND: Bovine Genital Campylobacteriosis (BGC), a worldwide distributed venereal disease caused by Campylobacter fetus subsp. venerealis (Cfv), has a relevant negative economic impact in cattle herds. The control of BGC is hampered by the inexistence of globally available effective vaccines. The present in silico study aimed to develop a multi-epitope vaccine candidate against Cfv through reverse vaccinology. RESULTS: The analysis of Cfv strain NCTC 10354 proteome allowed the identification of 9 proteins suitable for vaccine development. From these, an outer membrane protein, OmpA, and a flagellar protein, FliK, were selected for prediction of B-cell and T-cell epitopes. The top-ranked epitopes conservancy was assessed in 31 Cfv strains. The selected epitopes were integrated to form a multi-epitope fragment of 241 amino acids, which included 2 epitopes from OmpA and 13 epitopes from FliK linked by GPGPG linkers and connected to the cholera toxin subunit B by an EAAAK linker. The vaccine candidate was predicted to be antigenic, non-toxic, non-allergenic, and soluble upon overexpression. The protein structure was predicted and optimized, and the sequence was successfully cloned in silico into a plasmid vector. Additionally, immunological simulations demonstrated the vaccine candidate's ability to stimulate an immune response. CONCLUSIONS: This study developed a novel vaccine candidate suitable for further in vitro and in vivo experimental validation, which may become a useful tool for the control of BGC.


Subject(s)
Campylobacter Infections , Cattle Diseases , Vaccines , Animals , Cattle , Campylobacter Infections/prevention & control , Campylobacter Infections/veterinary , Vaccinology , Epitopes, T-Lymphocyte/chemistry , Genitalia , Computational Biology , Cattle Diseases/prevention & control
4.
Expert Rev Vaccines ; 23(1): 535-545, 2024.
Article in English | MEDLINE | ID: mdl-38664959

ABSTRACT

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/methods
5.
Int Immunopharmacol ; 133: 112120, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38657497

ABSTRACT

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 C
6.
Arch Microbiol ; 206(5): 217, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619666

ABSTRACT

The rodent-borne Arenavirus in humans has led to the emergence of regional endemic situations and has deeply emerged into pandemic-causing viruses. Arenavirus have a bisegmented ambisense RNA that produces four proteins: glycoprotein, nucleocapsid, RdRp and Z protein. The peptide-based vaccine targets the glycoprotein of the virus encountered by the immune system. Screening of B-Cell and T-Cell epitopes was done based on their immunological properties like antigenicity, allergenicity, toxicity and anti-inflammatory properties were performed. Selected epitopes were then clustered and epitopes were stitched using linker sequences. The immunological and physico-chemical properties of the vaccine construct was checked and modelled structure was validated by a 2-step MD simulation. The thermostability of the vaccine was checked followed by the immune simulation to test the immunogenicity of the vaccine upon introduction into the body over the course of the next 100 days and codon optimization was performed. Finally a 443 amino acid long peptide vaccine was designed which could provide protection against several members of the mammarenavirus family in a variety of population worldwide as denoted by the epitope conservancy and population coverage analysis. This study of designing a peptide vaccine targeting the glycoprotein of mammarenavirues may help develop novel therapeutics in near future.


Subject(s)
Arenaviridae , Vaccines , Humans , Arenaviridae/genetics , Vaccinology , Peptides , Epitopes/genetics , Glycoproteins
7.
Int J Biol Macromol ; 265(Pt 2): 130754, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38508555

ABSTRACT

The COVID-19 pandemic has emerged as a critical global health crisis, demanding urgent and effective strategies for containment. While some knowledge exists about epitope sequences recognized by human immune cells and their activation of CD8+ T cells within the HLA context, comprehensive information remains limited. This study employs reverse vaccinology to explore antigenic HLA-restricted T-cell epitopes capable of eliciting durable immunity. Screening reveals 187 consensus epitopes, with 23 offering broad population coverage worldwide, spanning over 5000 HLA alleles. Sequence alignment analysis highlights the genetic distinctiveness of these peptides from Homo sapiens and their intermediate to high TAP binding efficiency. Notably, these epitopes share 100 % sequence identity across strains from nine countries, indicating potential for a uniform protective immune response among diverse ethnic populations. Docking simulations further confirm their binding capacity with the HLA allele, validating them as promising targets for SARS-CoV-2 immune recognition. The anticipated epitopes are connected with suitable linkers and adjuvant, and then assessed for its translational efficacy within a bacterial expression vector through computational cloning. Through docking, it is observed that the chimeric vaccine construct forms lasting hydrogen bonds with Toll-like receptor (TLR4), while immune simulation illustrates an increased cytotoxic response aimed at CD8+ T cells. This comprehensive computational analysis suggests the chimeric vaccine construct's potential to provoke a robust immune response against SARS-CoV-2. By delineating these antigenic fragments, our study offers valuable insights into effective vaccine and immunotherapy development against COVID-19, contributing significantly to global efforts in combating this infectious threat.


Subject(s)
COVID-19 , Viral Vaccines , Humans , SARS-CoV-2 , COVID-19/prevention & control , Vaccinology , Pandemics/prevention & control , Molecular Docking Simulation , Epitopes, T-Lymphocyte/chemistry , Epitopes, B-Lymphocyte , Computational Biology , Vaccines, Subunit
8.
Vaccine ; 42(10): 2503-2518, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38523003

ABSTRACT

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-Lymphocyte
9.
Front Immunol ; 15: 1282754, 2024.
Article in English | MEDLINE | ID: mdl-38444851

ABSTRACT

Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs). Methods and results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. Conclusion: This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.


Subject(s)
Dengue , Vaccines , Virus Diseases , Humans , Vaccinology , Vaccination , Dengue/prevention & control
10.
Cell Rep Methods ; 4(3): 100731, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38490204

ABSTRACT

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 Simulation
11.
Ann Ig ; 36(4): 446-461, 2024.
Article in English | MEDLINE | ID: mdl-38436081

ABSTRACT

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/trends
13.
Microb Pathog ; 189: 106572, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38354987

ABSTRACT

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.


Subject(s)
JC Virus , Vaccines , Humans , Epitopes/genetics , Molecular Docking Simulation , Escherichia coli , Vaccinology , Vaccines, Subunit/genetics , Epitopes, T-Lymphocyte/genetics , Computational Biology , Epitopes, B-Lymphocyte , Molecular Dynamics Simulation
14.
BMC Infect Dis ; 24(1): 177, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38336665

ABSTRACT

BACKGROUND: Human polyomaviruses contribute to human oncogenesis through persistent infections, but currently there is no effective preventive measure against the malignancies caused by this virus. Therefore, the development of a safe and effective vaccine against HPyV is of high priority. METHODS: First, the proteomes of 2 polyomavirus species (HPyV6 and HPyV7) were downloaded from the NCBI database for the selection of the target proteins. The epitope identification process focused on selecting proteins that were crucial, associated with virulence, present on the surface, antigenic, non-toxic, and non-homologous with the human proteome. Then, the immunoinformatic methods were used to identify cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes from the target antigens, which could be used to create epitope-based vaccine. The physicochemical features of the designed vaccine were predicted through various online servers. The binding pattern and stability between the vaccine candidate and Toll-like receptors were analyzed through molecular docking and molecular dynamics (MD) simulation, while the immunogenicity of the designed vaccines was assessed using immune simulation. RESULTS: Online tools were utilized to forecast the most optimal epitope from the immunogenic targets, including LTAg, VP1, and VP1 antigens of HPyV6 and HPyV7. A multi-epitope vaccine was developed by combining 10 CTL, 7 HTL, and 6 LBL epitopes with suitable linkers and adjuvant. The vaccine displayed 98.35% of the world's population coverage. The 3D model of the vaccine structure revealed that the majority of residues (87.7%) were located in favored regions of the Ramachandran plot. The evaluation of molecular docking and MD simulation revealed that the constructed vaccine exhibits a strong binding (-1414.0 kcal/mol) towards the host's TLR4. Moreover, the vaccine-TLR complexes remained stable throughout the dynamic conditions present in the natural environment. The immune simulation results demonstrated that the vaccine design had the capacity to elicit robust immune responses in the host. CONCLUSION: The multi-parametric analysis revealed that the designed vaccine is capable of inducing sustained immunity against the selected polyomaviruses, although further in-vivo investigations are needed to verify its effectiveness.


Subject(s)
Polyomavirus , Vaccines , Humans , Molecular Docking Simulation , Vaccinology , Epitopes, T-Lymphocyte , Polyomavirus/genetics , Computational Biology/methods
15.
Biologicals ; 85: 101740, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38217963

ABSTRACT

Whooping cough is a disease caused by Bordetella pertussis, whose morbidity has increased, motivating the improvement of current vaccines. Reverse vaccinology is a strategy that helps identify proteins with good characteristics fast and with fewer resources. In this work, we applied reverse vaccinology to study the B. pertussis proteome and pangenome with several in-silico tools. We analyzed the B. pertussis Tohama I proteome with NERVE software and compared 234 proteins with B. parapertussis, B. bronchiseptica, and B. holmessi. VaxiJen was used to calculate an antigenicity value; our threshold was 0.6, selecting 84 proteins. The candidates were depurated and grouped in eight family proteins to select representative candidates, according to bibliographic information and their immunological response predicted with ABCpred, Bcepred, IgPred, and C-ImmSim. Additionally, a pangenome study was conducted with 603 B. pertussis strains and PanRV software, identifying 3421 core proteins that were analyzed to select the best candidates. Finally, we selected 15 proteins from the proteome study and seven proteins from the pangenome analysis as good vaccine candidates.


Subject(s)
Bordetella parapertussis , Whooping Cough , Humans , Bordetella pertussis/genetics , Whooping Cough/prevention & control , Proteome/metabolism , Vaccinology , Bordetella parapertussis/metabolism , Pertussis Vaccine
16.
Hum Vaccin Immunother ; 20(1): 2300157, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38198292

ABSTRACT

The 2nd China Vaccinology Integrated Innovation & Teaching Development Conference was held in Sun Yat-sen University, Shenzhen, 18-19, November 2023. Over 200 participants in the field of Vaccinology gathered together to address challenges and issues relevant to vaccine education and training courses, research, and public health programs in China. The conference themed "Promoting the Integrated and Innovative Development of Vaccinology through Collective Efforts." The conference was organized by the China Association of Vaccine (CAV) and hosted by Vaccinology Education Professional Committee of CAV, and School of Public Health (Shenzhen), Sun Yat-sen University. Other partners included the Medical Virology Branch of the Chinese Medical Association, the editorial committee of the Chinese Journal of Preventive Medicine, Human Vaccines & Immunotherapeutics, and the People's Medical Publishing House. The 1st conference was held in Hangzhou, in October 2020.


Subject(s)
Vaccines , Vaccinology , Humans , Health Education , Schools , China
17.
J Biomol Struct Dyn ; 42(3): 1293-1306, 2024.
Article in English | MEDLINE | ID: mdl-37054523

ABSTRACT

Visceral leishmaniasis (VL) is a tropical disease that causes severe public health problems in humans when untreated. As no licensed vaccine exists against VL, we aimed to formulate a potential MHC-restricted chimeric vaccine construct against this dreadful parasitic disease. Amastin-like protein derived from L. donovani is considered to be stable, immunogenic and non-allergic. A comprehensive established framework was used to explore the set of immunogenic epitopes with estimated population coverage of 96.08% worldwide. The rigorous assessment revealed 6 promiscuous T-epitopes which can plausibly be presented by more than 66 diverse HLA alleles. Further docking and simulation study of peptide receptor complexes identified a strong and stable binding interaction with better structural compactness. The predicted epitopes were combined with appropriate linkers and adjuvant molecules and their translation efficiency was evaluated in pET28+(a), an bacterial expression vector using in-silico cloning. Molecular docking followed by MD simulation study revealed a stable interaction between chimeric vaccine construct with TLRs. Immune simulation of the chimeric vaccine constructs showed an elevated Th1 immune response against both B and T epitopes. With this, the detailed computational analysis suggested that the chimeric vaccine construct can evoke a robust immune response against Leishmania donovani infection. Future studies are required to validate the role of amastin as a promising vaccine target.Communicated by Ramaswamy H. Sarma.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Vaccines , Humans , Leishmania donovani/genetics , Epitopes , Molecular Docking Simulation , Vaccinology , Leishmaniasis, Visceral/parasitology , Epitopes, T-Lymphocyte , Epitopes, B-Lymphocyte , Vaccines, Subunit , Computational Biology
18.
Immunol Res ; 72(1): 82-95, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37608125

ABSTRACT

Rickettsia prowazekii is an intracellular, obligate, gram-negative coccobacillus responsible for epidemic typhus. Usually, the infected body louse or its excrement when rubbed into the skin abrasions transmits the disease. The infection with R. prowazekii causes the highest death rate (> 20% without antibiotic treatment and now 1-7%), followed by epidemic typhus, which often manifests in unsanitary conditions (up to 15-30%). Conventionally, vaccine design has required pathogen growth and both assays (in vivo and in vitro), which are costly and time-consuming. However, advancements in bioinformatics and computational biology have accelerated the development of effective vaccine designs, reducing the need for traditional, time-consuming laboratory experiments. Subtractive genomics and reverse vaccinology have become prominent computational methods for vaccine model construction. Therefore, the RefSeq sequence of Rickettsia prowazekii (strain Madrid E) (Proteome ID: UP000002480) was subjected to subtractive genomic analysis, including factors such as non-similarity to host proteome, essentiality, subcellular localization, antigenicity, non-allergenicity, and stability. Based on these parameters, the vaccine design process selected specific proteins such as outer membrane protein R (O05971_RICPR PETR; OmpR). Eventually, the OmpR was subjected to a reverse vaccinology approach that included molecular docking, immunological simulation, and the discovery of B-cell epitopes and MHC-I and MHC-II epitopes. Consequently, a chimeric or multi-epitope-based vaccine was proposed by selecting the V11 vaccine and its 3D structure modeling along with molecular docking against TLR and HLA protein, in silico simulation, and vector designing. The obtained results from this investigation resulted in a new perception of inhibitory ways against Rickettsia prowazekii by instigating novel immunogenic targets. To further assess the efficacy and protective ability of the newly designed V11 vaccine against Rickettsia prowazekii infections, additional evaluation such as in vitro or in vivo immunoassays is recommended.


Subject(s)
Rickettsia prowazekii , Typhus, Endemic Flea-Borne , Typhus, Epidemic Louse-Borne , Humans , Proteomics , Rickettsia prowazekii/genetics , Rickettsia prowazekii/metabolism , Typhus, Epidemic Louse-Borne/microbiology , Molecular Docking Simulation , Proteome , Vaccinology/methods , Computational Biology/methods , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte/genetics , Vaccines, Subunit
19.
Int J Biol Macromol ; 258(Pt 1): 128753, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38104690

ABSTRACT

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.


Subject(s)
Arboviruses , Chikungunya Fever , Dengue , Vaccines , Zika Virus Infection , Zika Virus , Humans , Molecular Docking Simulation , Chikungunya Fever/prevention & control , Vaccines, Combined , Vaccinology/methods , Epitopes, T-Lymphocyte/chemistry , Computational Biology/methods , Epitopes, B-Lymphocyte , Vaccines, Subunit
20.
Ann Ist Super Sanita ; 59(4): 247-250, 2023.
Article in English | MEDLINE | ID: mdl-38088390

ABSTRACT

In recent times, especially as a result of the experience gained worldwide with the COVID19 pandemic vaccination campaigns, the personalization of vaccination strategies is becoming increasingly important. This does not yet mean bringing precision medicine and genomics approaches into immunization campaigns, but where there is more than one vaccine against the same disease, there is a need to identify criteria for personalizing vaccination.Vaccination strategies based on prescription appropriateness - whenever is possible - can lead to more effective immune response, reduced rates of adverse events, increased public confidence in vaccination and higher vaccination coverage, contributing to a decrease of morbidity and mortality related to preventable diseases.


Subject(s)
COVID-19 , Vaccines , Humans , Mass Vaccination , Vaccinology , COVID-19/prevention & control , Vaccination , Vaccines/adverse effects , Immunization Programs
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