Background and purpose: In 2019, the world has witnessed the emergence of a virus that caused acute respiratory distress syndrome in human with high mortality rates (approximately 3. 7%). So far, no effective treatment has been proven against COVID-19. This study aimed at designing a multiepitope vaccine combining several T-cell and B-cell epitopes of the SARS-CoV-2. Materials and methods: Based on immunoinformatics strategies, B-cell and T-cell epitopes were predicted using immune Epitope Database and Analysis Resource (IEDB). Then, the appropriate predicted epitopes were joined to each other by suitable linkers, and the multi-epitope vaccine constructed was suggested as a vaccine candidate against SARS-CoV-2. Results: In this study, 28 B-cell epitopes and 33 T-cell epitopes were predicted. Then, to design the multi epitope vaccine, 5 epitopes were used from the virion surface of spike protein and one epitope was used from intravirion region of the Envelope, Membrane, and Nucleocapsid proteins that later on were joined with flexible glycine linker. Conclusion: Based on the immunoinformatics results obtained, it seems that different epitopes from SARS-CoV-2 structural proteins have high ability to stimulate humoral and cellular immune responses, so the multi-epitope vaccine designed with these epitopes, can help to accelerate the production of effective vaccines against COVID-19.

Background and Objective: Acute Coronavirus Syndrome Virus (SARS-CoV-2) virus first appeared in China and spread rapidly around the world. Due to its wide spread around the world, efforts are needed to provide an effective and safe vaccine against this virus. The virus genome contains a single-stranded RNA molecule that encodes four different structural proteins, among which the virus spike (S) and nucleocapsid (N) proteins play an important role in stimulating the immune system to fight the virus. Multi-epitope peptide vaccines, which include immunogenic epitopes of T and B cells, have received much attention in recent years due to their high specificity. These vaccines were designed using immunoinformatics tools. Materials and Methods: In this study, the S and N proteins of SARSCoV-2 were analyzed with the help of bioinformatics servers to identify CD4 and B T cell epitopes. Cholera toxin B subunit and PADRE epitope were used as adjuvants. The components were linked together by peptide linkers and the structural features of the vaccine were predicted, including antigenicity, non-allergenicity, physicochemical properties, secondary and tertiary structures using bioinformatics servers. Results: According to the results of bioinformatics analysis, the structure has high antigenicity and is not allergenic. Conclusion: Therefore, the designed structure as a suitable vaccine candidate against SARS-CoV-2 can be examined, although experimental studies are necessary.

Background and Aim: Cutaneous leishmaniasis is a significant public health issue worldwide. Cutaneous leishmaniasis is the most prevalent in the world among the different types of leishmaniasis. Currently, available medications have had no discernible influence on the disease's progression. Up to now, there has been no approved cutaneous leishmaniasis vaccine. New developments in vaccination might be a potential way to come up with a vaccination that is successful for the treatment of cutaneous leishmaniasis. Materials and Methods: This research was conducted to learn more about an effective vaccine for Leishmania major, the ailment's primary cause of CL, which was designed using computational methods. Thus, a multiepitope protein was designed by utilizing potential immune system epitopes, including predicted MHC class I, MHC class II, Cytotoxic T lymphocytes, Bcell, and Interferon-gamma epitopes of Cysteine protease b (CPB), Leishmania homologue of activated C kinase (LACK), and Kinetoplastid membrane protein-11 (KMP-11) antigenic proteins. In order to enhance vaccine immunogenicity, two resuscitation-promoting factors of Mycobacterium tuberculosis were used as adjuvants. Final epitopes were matched with suitable linkers to construct the recombinant structure. The physicochemical and immune-based characteristics of the designed vaccine have been forecasted by using different tools. Moreover, homogeneity modeling was performed to obtain a high-quality 3D structure, followed by refinement and validation. Finally, the codon optimization based on E. coli resulted in a higher CAI value and optimal GC content, followed by combining it in the pET-14b cloning vector. Results: Evaluation of the various characteristics of the designed vaccine showed that it is an immunogenic and nonallergenic antigen that can induce immune responses against Leishmania major infection, which could be promising for cutaneous leishmaniasis. Conclusion: Research shows that a recombinant vaccine can be an effective candidate against cutaneous leishmaniasis.

Objective: Several vaccines against HIV have been investigated but none has been approved as an effective HIV vaccine. An approach that could induce stronger immune response against the pathogen is utilizing a multi-epitopic vaccine. This strategy was used in the design of several vaccines and resulted in improved immune responses.Materials and Methods: In this study a multi-epitopic fusion peptide including parts of HIV-1 Nef and P24 as a vaccine candidate was injected into mice and immune humoral responses measured with total antibody and IgG sub-classes using ELISA. Also measurement of cellular immune responses through evaluation of spleen cells proliferation response using MTT and cytotoxicity by LDH were performed. Finally, the cytokine pattern of IFN-g and IL-4 were also determined with ELISA.Results: The results indicate that candidate vaccine stimulated mouse splenic lymphocyte proliferation response and also induced strong cytotoxicity responses. Analysis of humoral immune response has shown that the candidate vaccine has induced specific antibody production mainly of the IgG2a sub-class. Also cytokine pattern evaluation has shown that IFN-g secretion was dominant.Conclusion: The use of immunogen and conserved epitopes from P24 and Nef induced strong humoral and cellular immune responses and this construct could be candidate for further studies in animal models.

Background: It is stated that in the absence of angiogenesis، the tumoral tissue will not grow beyond 2 mm3. Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis and blockade of this process could be applied as a novel strategy for immunotherapy of cancerMethods: Peptide sequences of VEGF-A isoforms were retrieved from protein databases and aligned. Immunodominant epitopes were determined and the selected one was rechecked for dissimilarity with other human proteins. The selected conserved peptide sequence was synthesized and conjugated with Keyhole limpet hemocyanin (KLH). Then، it was applied for immunization of mice. The polyclonal anti-VEGF antibody titer was measured using an indirect peptide-enzyme-linked immunosorbent assay (ELISA) with a Bovine serum albumin (BSA)-conjugated peptide.Findings: According to bioinformatic findings، the selected 41-aminoacid sequence did not show any similarity with other human proteins and revealed enough antigenicity to stimulate anti-tumor specific responses. A substantial increase of specific antibody titer was observed in vaccinated mice. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the BSA-conjugated peptide showed efficient coupling of the molecules. Optimization steps in ELISA procedures revealed that coating of microtiter plates with BSA-conjugated antigen provided more reproducible outcome than unconjugated peptide.Conclusion: Our results reinforce the potential of KLH-conjugated peptides for immunization and production of specific polyclonal antibodies against VEGF-A. Production of high-titer antibodies against this antigen indicates that the designed peptide-vaccine could be used as a potential immunogen for stimulation of humoral immune system in animal model.

Objective: Animal studies show that vaccination with epitope-based peptides results in protective immunity. However, immunodominance should be regarded as a major challenge in this area. Considering the advantages of epitopic-vaccines against hepatitis C virus (HCV) infection, herein, we compared the occurrence of immunodominance following mice immunization with three different HCV epitopic-peptide formulations.Methods: We synthesized four CD8+ epitopic-peptides (C1, E6, N, E4) that were derived from HCV-antigens. A polytope-peptide (C1E6NE4) spanning fusion of epitopes was designed based on immunoinformatics analyses for optimum proteasomal cleavage. BALB/c mice received three subcutaneous injections that contained 10 mg of peptide (minimal epitopes, or mixture of four epitopes or long-polytope) formulated with CpG (50 mg) and Montanide-ISA720 (70%) adjuvants in the tail-base at three-week intervals. Considering the H2-Dd (BALB/c)-restriction of C1 and E4-epitopes, three weeks after the last injection splenocytes from vaccinated animals were subjected to IFNg/IL4 ELISpot assays in the presence of C1 and E4-peptides.Results: All vaccinated animals promoted Th1-oriented responses as evidenced by detection of IFNg-secreting cells and a low-level of IL4 secretion. Mice injected with minimal CTL-epitopes provoked stronger responses, however, due to the higher affinity of E4-epitope for H2-Dd, frequency of E4-specific cells was considerably higher than C1-specific ones, showing some level of immunodominance. Interestingly, animals vaccinated with polytope-peptide developed high-quality balanced responses against both C1 and E4-epitopes, however at a lower intensity.Conclusion: These results supported the superiority of polytope-peptides over minimal epitopes, yet emphasized the key role of polytope design and optimization to avoid epitope dominancy.

Obesity and related disorders are among the leading causes of illness and mortality in the developed countries. To better understand the pathophysiological mechanisms that underlie metabolic disorders, increasing attention has been paid to central regulatory elements in energy homeostasis, including food intake behavior and energy expenditure. Ghrelin, a 28-amino acid peptide with an n-octanoylation indispensable for its biological activity, was originally discovered in rat stomach as the endogenous ligand for the growth hormone secretogogue (GHS) receptor (GHSR).The secretion of ghreline increases under conditions of negative energy balance, such as starvation, cachexia, and anorexia nervosa. Whereas its expression decreases under conditions of positive energy balance such as feeding, hyperglycemia, and obesity.

Background and Objectives: After live attenuated and subunit vaccines, DNA vaccines were introduced as a third generation vaccine in the field of vaccinology. This type of vaccine is a promising approach to deal with infectious agents in the future. Although, many aspects of this type of vaccine has not yet been identified, its use has been initiated in humans and clinical trials, and several DNA vaccines have been developed against veterinary infectious diseases. This generation of vaccine has provided new approaches to deal with and control existing diseases. In addition to infectious diseases, this type of vaccine can also be used against different types of tumors. Despite numerous attempts, only one type of DNA vaccine has been approved for use in human. The present study focuses on biology, advantages, and disadvantages of DNA vaccine and investigates its capacity in stimulating different types of immune responses.

For decades, nucleic acid analogues have been emerged in molecular biology. Some of these analogues are powerful bimolecular tools in biotechnology. Among the four major classes of these synthetic molecules (XNA: xenonucleic acid, LNA: locked nucleic acid, PNA: peptide nucleic acid and morpholino), PNA is the most important. In PNA, N-aminoethyle glycine units (to which purine/pyrimidine bases have been attached), are joined together to form an achiral and peptide-like structure that mimics the behavior of DNA and can hybridize to nucleic acid and to other PNA in sequence specific manner. Because of its unique physicochemical properties, PNA in many cases prefers over natural oligonucleotide and therefore, have been exploited in some strategies and methods in the field of diagnostics and therapy. In this review, we describe the structure, biochemical properties, and biomedical applications of PNA.