The BCG vaccine, advantages, and disadvantages of introducing new generation vaccines against Mycobacterium tuberculosis.

Tuberculosis (TB) is consistently ranked among the deadliest diseases worldwide, causing millions of deaths annually. Mycobacterium tuberculosis is the causative agent for this infection. Different antibiotics and vaccines have been discussed as potential treatments and prevention. Currently, there is only one licensed vaccine against TB, Bacillus Calmette-Guérin (BCG). Despite its protective efficacy against TB in children, BCG has failed to protect adults against pulmonary TB, lacks therapeutic value, and can cause complications in immunocompromised individuals. In this review, BCG, the most widely administered vaccine, is discussed, and the newest vaccines available in medicine are discussed. Based on the restrictions that prevent optimal BCG efficacy and the vaccines that are now being tested in various clinical studies, some criteria need to be considered in designing future vaccines.

Principle, application and challenges of development siRNA-based therapeutics against bacterial and viral infections: a comprehensive review.

While significant progress has been made in understanding and applying gene silencing mechanisms and the treatment of human diseases, there have been still several obstacles in therapeutic use. For the first time, ONPATTRO, as the first small interfering RNA (siRNA) based drug was invented in 2018 for treatment of hTTR with polyneuropathy. Additionally, four other siRNA based drugs naming Givosiran, Inclisiran, Lumasiran, and Vutrisiran have been approved by the US Food and Drug Administration and the European Medicines Agency for clinical use by hitherto. In this review, we have discussed the key and promising advances in the development of siRNA-based drugs in preclinical and clinical stages, the impact of these molecules in bacterial and viral infection diseases, delivery system issues, the impact of administration methods, limitations of siRNA application and how to overcome them and a glimpse into future developments.

In silico designing and immunoinformatics analysis of a novel peptide vaccine against metallo-beta-lactamase (VIM and IMP) variants.

The rapid spread of acquired metallo-beta-lactamases (MBLs) among gram negative pathogens is becoming a global concern. Improper use of broad-spectrum antibiotics can trigger the colonization and spread of resistant strains which lead to increased mortality and significant economic loss. In the present study, diverse immunoinformatic approaches are applied to design a potential epitope-based vaccine against VIM and IMP MBLs. The amino acid sequences of VIM and IMP variants were retrieved from the GenBank database. ABCpred and BCPred online Web servers were used to analyze linear B cell epitopes, while IEDB was used to determine the dominant T cell epitopes. Sequence validation, allergenicity, toxicity and physiochemical analysis were performed using web servers. Seven sequences were identified for linear B cell dominant epitopes and 4 sequences were considered as dominant CD4+ T cell epitopes, and the predicted epitopes were joined by KK and GPGPG linkers. Stabilized multi-epitope protein structure was obtained using molecular dynamics simulation. Molecular docking showed that the designed vaccine exhibited sustainable and strong binding interactions with Toll-like receptor 4 (TLR4). Finally, codon adaptation and in silico cloning studies were performed to design an effective vaccine production strategy. Immune simulation significantly provided high levels of immunoglobulins, T helper cells, T-cytotoxic cells and INF-γ. Even though the introduced vaccine candidate demonstrates a very potent immunogenic potential, but wet-lab validation is required to further assessment of the effectiveness of this proposed vaccine candidate.

Designing multi-epitope vaccine against important colorectal cancer (CRC) associated pathogens based on immunoinformatics approach.

BACKGROUND: It seems that several members of intestinal gut microbiota like Streptococcus bovis, Bacteroides fragilis, Helicobacter pylori, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, Peptostreptococcus anaerobius may be considered as the causative agents of Colorectal Cancer (CRC). The present study used bioinformatics and immunoinformatics approaches to design a potential epitope-based multi-epitope vaccine to prevent CRC with optimal population coverage. METHODS: In this study, ten amino acid sequences of CRC-related pathogens were retrieved from the NCBI database. Three ABCpred, BCPREDS and LBtope online servers were considered for B cells prediction and the IEDB server for T cells (CD4+ and CD8+) prediction. Then, validation, allergenicity, toxicity and physicochemical analysis of all sequences were performed using web servers. A total of three linkers, AAY, GPGPG, and KK were used to bind CTL, HTL and BCL epitopes, respectively. In addition, the final construct was subjected to disulfide engineering, molecular docking, immune simulation and codon adaptation to design an effective vaccine production strategy. RESULTS: A total of 19 sequences of different lengths for linear B-cell epitopes, 19 and 18 sequences were considered as epitopes of CD4+ T and CD8+ cells, respectively. The predicted epitopes were joined by appropriate linkers because they play an important role in producing an extended conformation and protein folding. The final multi-epitope construct and Toll-like receptor 4 (TLR4) were evaluated by molecular docking, which revealed stable and strong binding interactions. Immunity simulation of the vaccine showed significantly high levels of immunoglobulins, helper T cells, cytotoxic T cells and INF-γ. CONCLUSION: Finally, the results showed that the designed multi-epitope vaccine could serve as an excellent prophylactic candidate against CRC-associated pathogens, but in vitro and animal studies are needed to justify our findings for its use as a possible preventive measure.

Isolation of persister cells within the biofilm and relative gene expression analysis of type II toxin/antitoxin system in Pseudomonas aeruginosa isolates in exponential and stationary phases.

OBJECTIVES: Chronic infections and treatment failure are concerning issues in patients with Pseudomonas aeruginosa infections. Persister cell formation in biofilm is considered a key reason for antibiotic resistance and treatment failure. In this study, expression of type II toxin/antitoxin (TA) system genes (relBE, Xre-COG5654, vapBC and Xre-GNAT) in persister cells of biofilm was evaluated in the presence of the antibiotics ciprofloxacin and colistin during exponential and stationary phases. METHODS: The impact of antibiotics on biofilm persister cell formation during exponential and stationary phases of P. aeruginosa strains was examined by colony count at different time intervals in the presence of 5-fold minimum inhibitory concentration (MIC) of ciprofloxacin and colistin. Furthermore, expression of relBE, Xre-COG5654, vapBC and Xre-GNAT genes in P. aeruginosa strains undergoing antibiotic treatment for 3.5 h during exponential and stationary phases was examined by RT-qPCR. RESULTS: Formation of persister cells was observed in biofilms formed by P. aeruginosa strains in the presence of 5 × MIC of ciprofloxacin and colistin compared with the control group after 3.5 h of incubation both during exponential and stationary phases. The number of biofilm persister cells was higher in stationary phase than in exponential phase. According to the findings of RT-qPCR, ciprofloxacin and colistin may induce persister cell formation by enhancing the expression of type II TA systems during stationary and exponential phases. CONCLUSION: The result of this study indicate that ciprofloxacin and colistin have the potential to increase persister cells formation in biofilms by influencing the expression of type II TA systems.

An update review of globally reported SARS-CoV-2 vaccines in preclinical and clinical stages.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the rapidly spreading pandemic COVID-19 in the world. As an effective therapeutic strategy is not introduced yet and the rapid genetic variations in the virus, there is an emerging necessity to design, evaluate and apply effective new vaccines. An acceptable vaccine must elicit both humoral and cellular immune responses, must have the least side effects and the storage and transport systems should be available and affordable for all countries. These vaccines can be classified into different types: inactivated vaccines, live-attenuated virus vaccines, subunit vaccines, virus-like particles (VLPs), nucleic acid-based vaccines (DNA and RNA) and recombinant vector-based vaccines (replicating and non-replicating viral vector). According to the latest update of the WHO report on April 2nd, 2021, at least 85 vaccine candidates were being studied in clinical trial phases and 184 candidate vaccines were being evaluated in pre-clinical stages. In addition, studies have shown that other vaccines, including the Bacillus Calmette-Guérin (BCG) vaccine and the Plant-derived vaccine, may play a role in controlling pandemic COVID-19. Herein, we reviewed the different types of COVID-19 candidate vaccines that are currently being evaluated in preclinical and clinical trial phases along with advantages, disadvantages or adverse reactions, if any.