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The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes. Further, the physiochemical characterization was performed to check the aliphatic index, theoretical PI, molecular weight, and thermostable nature of vaccine construct. The allergenicity and antigenicity were also predicted to ensure the safety and immunogenic behavior of final vaccine construct. Moreover, homology modeling, followed by molecular docking and molecular dynamics simulation study was also performed to evaluate the binding affinity and stability of receptor (TLR-4) and ligand (vaccine protein) complex. This study warrants the experimental validation to ensure the immunogenicity and safety profile of presented vaccine construct which may be further helpful to control VL infection.

•The vaccine is composed of immunodominant regions of SARS-CoV-2 non-structural proteins.•Also, the functional region of the spike protein is incorporated in the vaccine construct.•The final vaccine construct contains multiple CD8+ and CD4+ overlapping epitopes•Also, it contains multiple IFN-γ inducing, linear and conformational B cell epitopes.•It forms significant interactions and stable complex with TLR-4/MD.•The DNA vaccine is designed by reverse translation of the final vaccine construct. SARS-CoV-2 causes a severe respiratory disease called COVID-19. Currently, global health is facing its devastating outbreak. However, there is no vaccine available against this virus up to now. In this study, a novel multi-epitope vaccine against SARS-CoV-2 was designed to provoke both innate and adaptive immune responses. The immunodominant regions of six non-structural proteins (nsp7, nsp8, nsp9, nsp10, nsp12 and nsp14) of SARS-CoV-2 were selected by multiple immunoinformatic tools to provoke T cell immune response. Also, immunodominant fragment of the functional region of SARS-CoV-2 spike (400–510 residues) protein was selected for inducing neutralizing antibodies production. The selected regions’ sequences were connected to each other by furin-sensitive linker (RVRR). Moreover, the functional region of β-defensin as a well-known agonist for the TLR-4/MD complex was added at the N-terminus of the vaccine using (EAAAK)3 linker. Also, a CD4 + T-helper epitope, PADRE, was used at the C-terminal of the vaccine by GPGPG and A(EAAAK)2A linkers to form the final vaccine construct. The physicochemical properties, allergenicity, antigenicity, functionality and population coverage of the final vaccine construct were analyzed. The final vaccine construct was an immunogenic, non-allergen and unfunctional protein which contained multiple CD8 + and CD4 + overlapping epitopes, IFN-γ inducing epitopes, linear and conformational B cell epitopes. It could form stable and significant interactions with TLR-4/MD according to molecular docking and dynamics simulations. Global population coverage of the vaccine for HLA-I and II were estimated 96.2% and 97.1%, respectively. At last, the final vaccine construct was reverse translated to design the DNA vaccine. Although the designed vaccine exhibited high efficacy in silico, further experimental validation is necessary.

Kaposi’s sarcoma-associated herpesvirus (KSHV) responsible for causing Kaposi sarcoma (KS), an opportunistic angioproliferative neoplasm is emerging rapidly. Despite this there is no permanent cure for this disease. The present study was aimed to design a multi-epitope based vaccine targeting the major glycoproteins of KSHV which plays an important role in the virus entry. After the application of rigorous immunoinformatics analysis and several immune filters, the multi-epitope vaccine was constructed, consisting of CD4, CD8 and IFN-γ inducing epitopes. Several physiochemical characteristics, allergenicity and antigenicity of the multi-epitope vaccine were analyzed in order to ensure its safety and immunogenicity. Further, the binding affinity and stability of the vaccine with Toll like receptor -9 (TLR-9) was analyzed by molecular docking and dynamics simulation studies. In addition, an in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a (+) vector. Such T-cell-based immunotherapies which leverage this mechanism could prove their potential against cancer. Further, the authors propose to test the present findings in the lab settings to ensure the safety, immunogenicity and efficacy of the presented vaccine which may help in controlling KSHV infection.

COVID-19 is a worldwide emergency; therefore, there is a critical need for foundational knowledge about B and T cell responses to SARS-CoV-2 essential for vaccine development. However, little information is available defining which determinants of SARS-CoV-2 other than the spike glycoprotein are recognized by the host immune system. In this study, we focus on the SARS-CoV-2 nucleocapsid protein as a suitable candidate target for vaccine formulations. Major B and T cell epitopes of the SARS-CoV-2 N protein are predicted and resulting sequences compared with the homolog immunological domains of other coronaviruses that infect human beings. The most dominant of B cell epitope is located between 176-206 amino acids in the SRGGSQASSRSSSRSRNSSRNSTPGSSRGTS sequence. Further, we identify sequences which are predicted to bind multiple common MHC I and MHC II alleles. Most notably there is a region of potential T cell cross-reactivity within the SARS-CoV-2 N protein position 102-110 amino acids that traverses multiple human alpha and betacoronaviruses. Vaccination strategies designed to target these conserved epitope regions could generate immune responses that are cross-reactive across human coronaviruses, with potential to protect or modulate disease. Finally, these predictions can facilitate effective vaccine design against this high priority virus.

Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine’s antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.

Cervical cancer is the fourth most common cancer among women worldwide, caused by the human papillomavirus (HPV). HPV16 /18 are strongly associated with the development of cervical cancer. HPV vaccines are not widely available in economically underdeveloped areas. They also have limited efficacy against pre-existing HPV infections and cervical lesions. Therefore, the study aims to computationally design a vaccine that induces both prophylactic and therapeutic immunity against cervical cancer. Using computational approaches, we designed a multi-epitope vaccine incorporating 62 cytotoxic T lymphocyte (CTL) epitopes, 7 helper T lymphocyte (HTL) epitopes, and 3 linear B-cell epitopes from conserved regions of HPV16/18 E6, E7, and L2 proteins. To increase immunogenicity, the adjuvant RS-09 (APPHALS) was added to the N-terminal of the vaccine. The chosen CTL and HTL epitopes have the potential to achieve 100% worldwide population coverage. The vaccine candidate has appropriate physicochemical properties. The vaccine’s secondary and tertiary structures were predicted, followed by refinement and validation of the models. The vaccine has a high affinity for Toll-like receptor 4 (TLR4), as indicated by its molecular docking score of -1164.4 kcal/mol and RMSD fluctuation range of 17 to 22.5 angstroms (Å) at the end of the MD simulation period. Immune response simulation showed that the vaccine candidate could induce strong humoral and cellular immune responses. The vaccine sequence’s GC content was calculated to be 48.99%, and subsequently, in silico cloning of the vaccine was performed in the pET28a (+) vector. The results reveal that this vaccine is highly immunogenic; however, experimental testing is required to confirm its efficacy and safety.

Background The spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers. Results The proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was − 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot and ProSA-web servers. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein sol and SOLpro servers indicating the solubility of the vaccine construct. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability. Docking of the vaccine construct with TLR4 demonstrated efficient binding energy with attractive binding energy of − 338.68 kcal/mol and − 346.89 kcal/mol for TLR4 chain A and chain B respectively. Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a(+) vector to ensure translational potency and microbial expression. Conclusion A unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.

Brucellosis and Tuberculosis, both of which are contagious diseases, have presented significant challenges to global public health security in recent years. Delayed treatment can exacerbate the conditions, jeopardizing patient lives. Currently, no vaccine has been approved to prevent these two diseases simultaneously. In contrast to traditional vaccines, mRNA vaccines offer advantages such as high efficacy, rapid development, and low cost, and their applications are gradually expanding. This study aims to develop multi-epitope mRNA vaccines argeting Brucella melitensis and Mycobacterium tuberculosis H37Rv (L4 strain) utilizing immunoinformatics approaches. The proteins Omp25, Omp31, MPT70, and MPT83 from the specified bacteria were selected to identify the predominant T- and B-cell epitopes for immunological analysis. Following a comprehensive evaluation, a vaccine was developed using helper T lymphocyte epitopes, cytotoxic T lymphocyte epitopes, linear B-cell epitopes, and conformational B-cell epitopes. It has been demonstrated that multi-epitope mRNA vaccines exhibit increased antigenicity, non-allergenicity, solubility, and high stability. The findings from molecular docking and molecular dynamics simulation revealed a robust and enduring binding affinity between multi-epitope peptides mRNA vaccines and TLR4. Ultimately, Subsequently, following the optimization of the nucleotide sequence, the codon adaptation index was calculated to be 1.0, along with an average GC content of 54.01%. This indicates that the multi-epitope mRNA vaccines exhibit potential for efficient expression within the Escherichia coli(E . coli) host. Analysis through immune modeling indicates that following administration of the vaccine, there may be variation in immunecell populations associated with both innate and adaptive immune reactions. These types encompass helper T lymphocytes (HTL), cytotoxic T lymphocytes (CTL), regulatory T lymphocytes, natural killer cells, dendritic cells and various immune cell subsets. In summary, the results suggest that the newly created multi-epitope mRNA vaccine exhibits favorable attributes, offering novel insights and a conceptual foundation for potential progress in vaccine development.

Currently, HIV (human immunodeficiency virus) infection is one of the leading complications in public health and causes acquired immunodeficiency syndrome (AIDS), especially in the African region. No specific vaccine is available to combat this, with multi-strain variability being one of the hurdles. In this investigation, we employed variability in the epitope of the HIV subtype C targets to introduce mutations and construct an epitope-based vaccine. Four targets were examined to predict the B and T cells (major histocompatibility complex class I and II). Among the predicted epitopes, immunodominant epitopes were selected and were mapped with the identified variable amino acid to incorporate mutation. These selected and mutated epitopes were used for the non-mutated and mutated vaccine construction, considering linker for fusion and adjuvant to improve the activity. The vaccine’s structure was modeled and examined to validate its structural quality, and a high population coverage was also found. The docking investigation of the non-mutated and mutated vaccine with Toll-like receptor 3 shows remarkable activity followed by strong binding affinity, and the simulation of over 100 ns revealed the constancy of the complex system. The immune response revealed its strong effectiveness by generating multiple immunoglobulins followed by the time step of infection, and further, in silico cloning demonstrated a high expression in Escherichia coli based on their favorable Codon Adaptation Index and GC value. The integrated approach in this investigation will help to plan a potent immunodominant vaccine that can work for multiple strains of HIV infection.