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... of the refined vaccine. A total of 98 pair of residue useful for disulfide engineering was found, from which ten pairs (PRO511-SER532 ARG574-TYR577 ARG48-GLY77 ASP587-TYR602 SER597-SER601 VAL106-GLY543 ALA593-ARG598 PRO168-GLU566 GLY51-ASN514 MET64-ARG69) were selected on the ground of their energy, Chi3 value and high B-factor as shown in Fig. ...
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... The selected HTL epitopes excel due to their ability to stimulate interferon (IFN-γ), interleukin-4 (IL-4) and interleukin-10 (IL-10) production. The cytokines are crucial for stimulating the activation and maturation of T-helper 1 and T-helper 2 cells, respectively [52] suggesting that our vaccine construct can promote the release of essential cytokines. The prediction of each of the epitope's antigenicity, toxicity, and allergenicity helped ensure that the vaccine candidate was safe, effective, and capable of stimulating an appropriate immune response. ...
... The orientation of protein folding can be determined by the results of the secondary structure [50,52]. The primary vaccine construct was inputted into an appropriate server to predict and analyze its secondary structure. ...
Background: Influenza D Virus (IDV) presents a possible threat to animal and human health, necessitating the development of effective vaccines. Although no human illness linked to IDV has been reported, the possibility of human susceptibility to infection remains uncertain. Hence, there is a need for an animal vaccine to be designed. Such a vaccine will contribute to preventing and controlling IDV outbreaks and developing effective countermeasures against this emerging pathogen. This study, therefore, aimed to design an mRNA vaccine construct against IDV using immunoinformatic methods and evaluate its potential efficacy. Methods: A comprehensive methodology involving epitope prediction, vaccine construction, and structural analysis was employed. Viral sequences from six continents were collected and analyzed. A total of 88 Hemagglutinin Esterase Fusion (HEF) sequences from IDV isolates were obtained, of which 76 were identified as antigenic. Different bioinformatics tools were used to identify preferred CTL, HTL, and B-cell epitopes. The epitopes underwent thorough analysis, and those that can induce a lasting immunological response were selected for the construction. Results: The vaccine prototype comprised nine epitopes, an adjuvant, MHC I-targeting domain (MITD), Kozaq, 3′ UTR, 5′ UTR, and specific linkers. The mRNA vaccine construct exhibited antigenicity, non-toxicity, and non-allergenicity, with favourable physicochemical properties. The secondary and tertiary structure analyses revealed a stable and accurate vaccine construct. Molecular docking simulations also demonstrated strong binding affinity with toll-like receptors. Conclusions: The study provides a promising framework for developing an effective mRNA vaccine against IDV, highlighting its potential for mitigating the global impact of this viral infection. Further experimental studies are needed to confirm the vaccine’s efficacy and safety.
... Five epitopes consisted one BCE and four TCE were shortlisted that were ranked by immunogenicity score, and were then subjected to physico-chemical properties analysis. It is important to analyze the properties of the epitopes of both B-cell and T-cell epitopes for effective delivery and to stimulate specific immune responses (Oladipo et al., 2020). The physico-chemical properties that are important include the size, stability, solubility and hydrophobicity of the epitopes. ...
... Different groups focused on studies of multiepitope vaccines against various TLRs. For instance, Oladipo et al. 90 studied the TLR2, TLR3, TLR4, and TLR9, while Rafi et al. 91 focused on TLR2 and TLR4, and Ysrafil et al. 92 investigated TLR3, TLR4, and TLR8, as well as angiotensin-converting enzyme 2 (ACE2) as the entry receptors of SARS-CoV-2. Drawing upon the structure of the SARS-CoV-2 spike (S) glycoprotein (and nucleocapsid (N) protein and open reading frame 1a (ORF1a) protein in the case of Ysrafil et al. 92 ), the authors tried to develop a potent multiepitope subunit vaccine. ...
... The stability of the complexes of various vaccines was confirmed by studying their dynamic properties. For instance, Oladipo et al. 90 and Pitaloka et al. 93 used NMA to study the stability and mobility of selected receptor−vaccine complexes. In the first study, as a result, the vaccine protein and its receptor were predicted to spin toward each other. ...
Toll-like receptors (TLRs) are transmembrane proteins that recognize various molecular patterns and activate signaling that triggers the immune response. In this review, our goal is to summarize how, in recent years, various computational solutions have contributed to a better understanding of TLRs, regarding both their function and mechanism of action. We update the recent information about small-molecule modulators and expanded the topic toward next-generation vaccine design, as well as studies of the dynamic nature of TLRs. Also, we underline problems that remain unsolved.
... The above-mentioned protocol and its variations have been used multiple times for vaccine design. Undoubtedly, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received the most attention in recent years [80][81][82][83] . However, studies on other vaccine designs have also been carried out, both before and after the outbreak of COVID- 19 95,96 . ...
... The stability of the complexes was confirmed by studying their dynamic properties. For instance, Oladipo et al.80 and Pitaloka et al.83 [58] used NMA to study the stability and mobility of selected receptor-vaccine complexes. In the first study, as a result, the vaccine protein and its receptor were predicted to spin towards each other.In the second study, based on the detected correlations in the covariance matrix between pairs of residues, the authors confirmed the stability of the vaccine candidate model.Rafi et al.81 performed classical MD simulations to check the stability of the constructed vaccine with the extracellular subunit of TLR2 and TLR4/MD2. ...
Toll-like receptors (TLRs) are transmembrane proteins which recognise various molecular patterns and activate signalling that triggers the immune response. In this review, our goal was to summarise how, in recent years, various computational solutions contributed to a better understanding of TLRs, regarding both their function and mechanism of action. We updated the recent information about small-molecule modulators and expanded the topic towards next- generation vaccine design, as well as studies of the dynamic nature of TLRs. Also, we underlined problems which remain unsolved.
... The multiple-epitope vaccine approach has been shown to be promising against Influenza A virus (Maleki et al., 2022), SARS-CoV-2 Kar et al., 2020;Oladipo et al., 2020;Yang et al., 2021), Zika virus , Mycobacterium tuberculosis (Bibi et al., 2021), and Pseudomonas aeruginosa (Dey et al., 2022). Recently, multi epitope vaccine construct has been developed against Toxoplasma gondii and it showed promising results in invivo and invitro experiments. ...
Streptococcus pneumonia, the causative agent of sepsis, meningitis and pneumonia, is held responsible for causing invasive diseases predominantly in children along with adults from both developing and developed countries. The available vaccines coverage in the context of different serotypes is limited and emergence of non-vaccine serotypes could further emerge as a threat in future. Advanced immunoinformatics tools have been used for developing a multi epitope subunit vaccine. In the current study we have subjected these four surface antigenic proteins Ply, PsaA, PspA and PspK to construct vaccine designs. We have predicted different B-cell and T-cell epitopes by using NetCTL 1.2, IEDB (Immune Epitope Databases) and ABCpred. An adjuvant (griselimycin) has been added to the vaccine construct sequence in order to improve its immunogenicity. The vaccine construct has been evaluated for its antigenicity, allergenicity, toxicity and different physio-chemical properties. The bioinformatic tools have been used for prediction, refinement and validation of the 3 D structure. Further, the vaccine structure has been docked with a toll-like receptor (TLR-4) by ClusPro 2.0. In conclusion, the proposed multi-epitope vaccine designs could potentially activate both humoral and cellular immune responses and has a potential to be a vaccine candidate against S.pneumoniae, and requires experimental validation for ensuring immunogenicity and safety profile.
Communicated by Ramaswamy H. Sarma
... Studies demonstrated that an epitope-based peptide vaccine against SARS-CoV-2 was docked effectively with TLR5 and it enhanced the binding affinity. TLR2, TLR3, TLR4, and TLR9 were tested by molecular docking with the help of the ClusPro 2.0 protein-protein docking server [325,326]. In another study, TLR5-coronavirus spike protein S1 subunit was used to make recombinant subunit vaccines against SARS-CoV-2 [313,327]. ...
The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the potential available therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary approaches for countering SARS-CoV-2.
... With an isoelectric point of 9.85, the VC shows basicity and this determines its electrophoretic mobility and consequently its purification [28]. With an instability index less than 40, the VC is predicted to be stable after expression [29] and it is also thermo-stable across wide temperature range due to high aliphatic index [29]. A negative GRAVY value indicates that the VC is non-polar suggesting depicting hydrophobicity [29]. ...
... With an isoelectric point of 9.85, the VC shows basicity and this determines its electrophoretic mobility and consequently its purification [28]. With an instability index less than 40, the VC is predicted to be stable after expression [29] and it is also thermo-stable across wide temperature range due to high aliphatic index [29]. A negative GRAVY value indicates that the VC is non-polar suggesting depicting hydrophobicity [29]. ...
... With an instability index less than 40, the VC is predicted to be stable after expression [29] and it is also thermo-stable across wide temperature range due to high aliphatic index [29]. A negative GRAVY value indicates that the VC is non-polar suggesting depicting hydrophobicity [29]. ...
Purpose: Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC).
Materials and Methods: The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropri- ate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engi- neering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector.
Results: A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubil- ity upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimat- ed half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS.
Conclusion: The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.
Keywords: Lassa virus, Envelope protein, Major histocompatibility complex, Epitopes, Vaccine candidate
... Supported by the current literature, we developed a potential vaccine candidate against L. donovani. Imperatively, several studies have employed in silico techniques in the design of potential vaccines/drugs against various diseases [53][54][55][56]. These in silico techniques effectively predict epitopes without wasting time and they have no expenses, unlike experimental screenings that are costly and time-consuming. ...
Leishmaniasis is a neglected tropical disease caused by parasitic intracellular protozoa of the genus Leishmania. The visceral form of this disease caused by Leishmania donovani continues to constitute a major public health crisis, especially in countries of endemicity. In some cases, it is asymptomatic and comes with acute and chronic clinical outcomes such as weight loss, pancytopenia, hepatosplenomegaly, and death if left untreated. Over the years, the treatment of VL has relied solely on chemotherapeutic agents, but unfortunately, these drugs are now faced with challenges. Despite all efforts, no successful vaccine has been approved for VL. This could be as a result of limited knowledge/understanding of the immune mechanisms necessary to regulate parasite growth. Using a computational approach, this study explored the prospect of harnessing the properties of a disulfide isomerase protein of L. donovani amastigotses to develop a multi-epitope subunit vaccine candidate against the parasite. We designed a 248-amino acid multi-epitope vaccine with a predicted antigenicity probability of 0.897372. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was stable, non-allergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against Leishmania spp. Parasites.
... As of 20 January 2022, 336,790,193 cases of COVID-19 and 5,560,718 deaths [2] were confirmed. The RNA of the virus SARS-CoV-2, of the family coronaviridae, possesses a spike (S) glycoprotein, which extends over the surface of the virus to initiate the insemination of coronavirus into the host cells [3,4]. On this glycoprotein, there are 14 residue-binding receptors, which communicate with the angiotensin-converting-enzyme 2 (ACE2) receptor [5]. ...
... On this glycoprotein, there are 14 residue-binding receptors, which communicate with the angiotensin-converting-enzyme 2 (ACE2) receptor [5]. Coronavirus spike glycoprotein has acceptable antigenicity and immunogenicity [3,6]. ...
... High measures of IgM, IgG1, and IgG3 antibodies were discovered after administering the vaccine, and prolonged immune responses against the virus were evident through High measures of IgM, IgG1, and IgG3 antibodies were discovered after administering the vaccine, and prolonged immune responses against the virus were evident through high measures of IgG and IgM immunoglobulins. Furthermore, simulation statistics revealed that an amino acid sequence revealed that cytotoxic T-cells' elevation, after 13 days of administering vaccine, attained a maximum of 1155 cells per mm 3 . This value gradually decreased to 1120 cells per mm 3 after 33 days. ...
This article is devoted to applying bioinformatics and immunoinformatics approaches for
the development of a multi-epitope mRNA vaccine against the spike glycoproteins of circulating SARS-CoV-2 variants in selected African countries. The study’s relevance is dictated by the fact that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began its global threat at the end of 2019 and since then has had a devastating impact on the whole world. Measures to reduce threats from the pandemic include social restrictions, restrictions on international travel, and vaccine development. In most cases, vaccine development depends on the spike glycoprotein, which serves as a medium for its entry into host cells. Although several variants of SARS-CoV-2 have emerged from mutations crossing continental boundaries, about 6000 delta variants have been reported along the coast of more than 20 countries in Africa, with South Africa accounting for the highest percentage. This also applies to the omicron variant of the SARS-CoV-2 virus in South Africa. The authors suggest that bioinformatics and immunoinformatics approaches be used to develop a multi-epitope mRNA vaccine against the spike glycoproteins of circulating SARS-CoV-2 variants in selected African countries. Various immunoinformatics tools have been used to predict T- and B-lymphocyte epitopes.
The epitopes were further subjected to multiple evaluations to select epitopes that could elicit a sustained immunological response. The candidate vaccine consisted of seven epitopes, a highly immunogenic adjuvant, an MHC I-targeting domain (MITD), a signal peptide, and linkers. The molecular weight (MW) was predicted to be 223.1 kDa, well above the acceptable threshold of 110 kDa on an excellent vaccine candidate. In addition, the results showed that the candidate vaccine was antigenic, non-allergenic, non-toxic, thermostable, and hydrophilic. The vaccine candidate has good population coverage, with the highest range in East Africa (80.44%) followed by South Africa (77.23%). West Africa and North Africa have 76.65% and 76.13%, respectively, while Central Africa (75.64%) has minimal coverage. Among seven epitopes, no mutations were observed in 100 randomly
selected SARS-CoV-2 spike glycoproteins in the study area. Evaluation of the secondary structure of the vaccine constructs revealed a stabilized structure showing 36.44% alpha-helices, 20.45% drawn filaments, and 33.38% random helices. Molecular docking of the TLR4 vaccine showed that the simulated vaccine has a high binding affinity for TLR-4, reflecting its ability to stimulate the innate and adaptive immune response.
... This failure is partly owing to inadequate knowledge relating to Chlamydia immune response as well as lack of adequate information about the required immunological components necessary for treating Chlamydia infections and protection against reinfection [7,23]. Several research works propose that humoral as well as cell-initiated immunity are required to develop vaccine for Chlamydia prevention and subunit vaccines has been the focus of contemporary researchers as compared to earlier studies that focus on whole organisms, this is because subunit vaccines comprises target immunogenic factor of the infectious agents responsible for the disease rather than using the whole infectious organisms [69]. This has become possible as genomic and proteomic information of microorganisms are now readily available on several online servers and databases, hence a priori identification of potential antigenic targets through epitope prediction using computational approaches is now achievable by using the information from these databases [40]. ...
... This is vital in developing vaccines based on multi-epitope subunits [32,33,40]. In our study, it was observed that the GC-content of the enhanced vaccine peptide sequence was 53.75% and the codon adaptation index was 1.0, this was a satisfactory adaptation achieved and it aligned favorably with result reported by other researchers who stated that vaccine candidates with data of this kind are significant for development of active vaccine that can elicit immunological responses [40,42,69]. The potential industrial production of the vaccine must be evaluated to identify suitable vectors for large scale production; this is investigated on the SnapGen online tool [40,69]. ...
... In our study, it was observed that the GC-content of the enhanced vaccine peptide sequence was 53.75% and the codon adaptation index was 1.0, this was a satisfactory adaptation achieved and it aligned favorably with result reported by other researchers who stated that vaccine candidates with data of this kind are significant for development of active vaccine that can elicit immunological responses [40,42,69]. The potential industrial production of the vaccine must be evaluated to identify suitable vectors for large scale production; this is investigated on the SnapGen online tool [40,69]. The vaccine nucleotide sequence obtained from in silico adaptation insert between the restriction site XhoI and NdeI resulting in a 7.02kbp long ...
Chlamydia trachomatis serovars A, B, Ba and C are bacteria serovars responsible for the blinding disease trachoma, the infection affects the upper tarsal conjunctiva of the eye. Repeated infection occurs among people in endemic areas throughout childhood which may later lead to blindness at adulthood. Chlamydia trachomatis contains a highly conserved surface glycoprotein, the polymorphic membrane protein which are surface antigens and are target for neutralizing antibodies as they are strongly immunogenic hence elicit proinflammatory response. It is suggested that they may be virulence by modulating inflammation and adherence to host cell, therefore one can argue that PMPs may be important in host-cell invasion as a virulence factor; this fact makes it a good entrant for Chlamydia trachomatis vaccine design.
In this study a combination of bioinformatics and immunoinformatics methods and tools were applied to design multi-epitope subunit vaccines using Chlamydia trachomatis polymorphic membrane protein G (PMPG). The vaccine candidate was constructed using suitable linkers to link the CTL epitopes, HTC epitopes and adjuvant together, this constructed vaccine candidate was appraised for its antigenic and allergenic properties, the physicochemical parameters which include the molecular formula, theoretical isoelectric point (pI), molecular weight, half-life, instability index, solubility score, GRAVY and aliphatic index were also predicted. The vaccine secondary structure was predicted to evaluate the properties of the secondary structure of the vaccine such as the helices, sheets and coils. The tertiary structure was also predicted, refined and validated using data like Ramachandran plot and Z-score. Disulfide engineering was executed in regions having high mobility in order to improve the protein stability of the candidate vaccine, from this, three pairs of amino acid residues GLY112-THR135, TYR137-ARG139 and THR144-ASN147 were finalized based on their chi3 and B-factor value. Codon adaptation carried out revealed that the vaccine candidate sequence has a GC-content of 53.75% and codon adaptation index of 1.0. In silico cloning was also carried out to determine the vector and cloning site suitable for overproduction of the vaccine protein for large scale production process. To determine the complex stability and binding free energy of the vaccine candidate, molecular docking was performed using the vaccine protein as ligand while TLR-2 and TLR-4 were the receptors. The lowest binding energy for the vaccine-TLR4 complex was −1626.7 and −1305.1 for the vaccine-TLR2 complex. Dynamic simulation provided predictions such as eigenvalue of 5.277774 × 10⁻⁰⁶ for TLR-4 receptor and 7.403984 × 10⁻⁰⁶ for TLR-2 receptor. From results obtained from the various predictions and validations, it can be concluded that the candidate vaccine will be capable of inducing anti-inflammatory immunity which may be able to prevent Chlamydia trachomatis invasion among human hosts.
