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Candida dubliniensis is an opportunistic pathogen associated with oral and invasive fungal infections in immune-compromised individuals. Furthermore, the emergence of C. dubliniensis antifungal drug resistance could exacerbate its treatment. Hence, in this study a multi-epitope vaccine candidate has been designed using an immunoinformatics approach by targeting C. dubliniensis secreted aspartyl proteinases (SAP) proteins. In silico tools have been utilized to predict epitopes and determine their allergic potential, antigenic potential, toxicity, and potential to elicit interleukin-2 (IL2), interleukin-4 (IL4), and IFN-γ. Using the computational tools, eight epitopes have been predicted that were then linked with adjuvants for final vaccine candidate development. Computational immune simulation has depicted that the immunogen designed emerges as a strong immunogenic candidate for a vaccine. Further, molecular docking and molecular dynamics simulation analyses revealed stable interactions between the vaccine candidate and the human toll-like receptor 5 (TLR5). Finally, immune simulations corroborated the promising candidature of the designed vaccine, thus calling for further in vivo investigation. [ABSTRACT FROM AUTHOR]

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as live attenuated vaccinia virus-based vaccines, which pose challenges of safety and efficacy in chronic infections. In this study, we have used an immunoinformatics-aided design of a multi-epitope vaccine (MEV) candidate by targeting monkeypox virus (MPXV) glycoproteins and membrane proteins. From these proteins, seven epitopes (two T-helper cell epitopes, four T-cytotoxic cell epitopes and one linear B cell epitopes) were finally selected and predicted as antigenic, non-allergic, interferon-γ activating and non-toxic. These epitopes were linked to adjuvants to design a non-allergic and antigenic candidate MPXV-MEV. Further, molecular docking and molecular dynamics simulations predicted stable interactions between predicted MEV and human receptor TLR5. Finally, the immune-simulation analysis showed that the candidate MPXV-MEV could elicit a human immune response. The results obtained from these in silico experiments are promising but require further validation through additional in vivo experiments. [ABSTRACT FROM AUTHOR]

Background: Candida tropicalis causes tropical invasive fungal infections, with a high mortality. This fungus has been found to be resistant to antifungal classes such as azoles, echinocandins, and polyenes in several studies. As a result, it is vital to identify novel approaches to prevent and treat C. tropicalis infections. In this study, an in silico technique was utilized to deduce and evaluate a powerful multivalent epitope-based vaccine against C. tropicalis, which targets the secreted aspartic protease 2 (SAP2) protein. This protein is implicated in virulence and host invasion. Results: By focusing on the Sap2 protein, 11 highly antigenic, non-allergic, non-toxic, and conserved epitopes were identified. These were subsequently paired with RS09 and flagellin adjuvants, as well as a pan HLA DR-binding epitope (PADRE) sequence to create a vaccine candidate that elicited both cell-mediated and humoral immune responses. It was projected that the vaccine design would be soluble, stable, antigenic, and non-allergic. Ramachandran plot analysis was applied to validate the vaccine construct's 3-dimensional model. The vaccine construct was tested (at 100 ns) using molecular docking and molecular dynamics simulations, which demonstrated that it can stably connect with MHC-I and Toll-like receptor molecules. Based on in silico studies, we have shown that the vaccine construct can be expressed in E. coli. We surmise that the vaccine design is unrelated to any human proteins, indicating that it is safe to use. Conclusions: The vaccine design looks to be an effective option for preventing C. tropicalis infections, based on the outcomes of the studies. A fungal vaccine can be proposed as prophylactic medicine and could provide initial protection as sometimes diagnosis of infection could be challenging. However, more in vitro and in vivo research is needed to prove the efficacy and safety of the proposed vaccine design. [ABSTRACT FROM AUTHOR]

Background: Canine circovirus is a deadly pathogen of dogs and causes vasculitis and hemorrhagic enteritis. It causes lethal gastroenteritis in pigs, fox, and dogs. Canine circovirus genome contains two main (and opposite) transcription units which encode two open reading frames (ORFs), a replicase-associated protein (Rep) and the capsid (Cap) protein. The replicase protein and capsid protein consist of 303 amino acids and 270 amino acids respectively. Several immuno-informatics methods such as epitope screening, molecular docking, and molecular-dynamics simulations were used to craft peptide-based vaccine construct against canine circovirus. Results: The vaccine construct was designed by joining the selected epitopes with adjuvants by suitable linker. The cloning and expression of the vaccine construct was also performed using in silico methods. Screening of epitopes was conducted by NetMHC server that uses ANN (Artificial neural networking) algorithm. These methods are fast and cost-effective for screening epitopes that can interact with dog leukocyte antigens (DLA) and initiate an immune response. Overall, 5 epitopes, YQHLPPFRF, YIRAKWINW, ALYRRLTLI, HLQGFVNLK, and GTMNFVARR, were selected and used to design a vaccine construct. The molecular docking and molecular dynamics simulation studies show that these epitopes can bind with DLA molecules with stability. The codon adaptation and in silico cloning studies show that the vaccine can be expressed by Escherichia coli K12 strain. Conclusion: The results suggest that the vaccine construct can be useful in preventing the dogs from canine circovirus infections. However, the results need further validation by performing other in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

[Display omitted] • Anepitope vaccine was designed against Human Cytomegalovirus by in silico method. • The vaccine consists of T-cell epitopes and adjuvants joined by GGS linker. • The vaccine is non-allergic, antigenic , and has good physiochemical properties. • Molecular docking and simulation showed the vaccine interacts with stability to Toll like receptor. • In silico cloning shows that the vaccine can be cloned in E. coli K12 strain. Human Cytomegalovirus (HCMV) is one of the most common causes of congenital infections globally. They infect the fetus and cause severe birth defects such as hearing loss, complications in the eyes, epilepsy, autism, and various other neurological disorders. They are also the leading cause of death in patients with compromised immunity. Due to the prevalence and severity of the virus, the United States National Academy of Medicine has announced the development of the HCMV vaccine as a matter of high priority for public health. Hence, this study is focused on designing a novel potent multi-epitope HCMV vaccine. The envelope glycoproteins B, H, L and M of HCMV were targeted to predict T cell (both Helper and Cytotoxic) epitopes that were non-toxic, highly antigenic, and non-allergenic and could induce interferon-γ production. Further, the selected epitopes were subjected to molecular docking and population coverage analysis. Eventually, using the two best epitopes and adjuvants like RS09, flagellin protein and PADRE sequence a 283 amino acid long vaccine was designed. The vaccine is antigenic, non-allergenic, stable, and soluble. The 3D model of the vaccine was developed and validated using the Ramachandran plot. Docking with Toll-like receptor 5 (TLR5) molecule and molecular dynamics simulation confirmed the stability of the vaccine. In silico cloning simulation using pET28a (+) vector showed that the vaccine can be successfully cloned and expressed in E. coli K12 strain. However, the efficacy and the safety of the vaccine need to be further validated by in vivo studies. [ABSTRACT FROM AUTHOR]

Candida auris is a rapidly emerging human pathogenic fungus with a high mortality rate. Recent report suggests that the new clinical isolates are showing resistance to the major classes of antifungal drugs. Due to the emergence of drug resistance, it becomes imperative to seek novel therapies for the treatment of C. auris. The potent vaccine could be one of the promising strategies for recalcitrant and multidrug-resistant pathogens. Using in silico approach we designed a novel multivalent vaccine against C. auris. We have selected the agglutinin-like sequence-3 (Als3) an adhesion protein, involved in virulence. The Als3p protein of C. auris was targeted to predict T cell and B cell epitopes. Epitopes which were found to be non-toxic, non-allergenic, highly conserved, and antigenic and could induce interferon-γ synthesis were selected for vaccine design. The selected epitopes were linked with suitable adjuvants to construct the final vaccine. The vaccine construct was predicted to be stable, soluble, antigenic, non-allergic with desirable physicochemical properties. We also constructed the 3D model of the vaccine and validated it with the Ramachandran plot. The ability of the vaccine construct to interact with Toll-like receptor (TLR) and major histocompatibility complex (MHC) was determined by molecular docking experiments. The binding energy of the vaccine construct with the TLR and MHC were found to be stable as predicted by molecular dynamics simulation. Further, in-silico cloning analysis showed that the vaccine construct can be successfully cloned and expressed in E. coli. Based on the results, we surmise that our candidate vaccine can be used as an alternative therapy for the treatment of C. auris. However, the efficacy and the safety of the vaccine model need to be determined by performing in vivo studies. • Candida auris is a rapidly emerging human pathogenic fungus with high mortality rate. • A multi-epitope subunit-based vaccine against C. auris is designed using in-silico tools. • The vaccine was constructed using 8 highly antigenic epitopes, PADRE sequence, and adjuvant linked together by GGS linker. • The results show that the vaccine construct is highly antigenic but at the same time non-toxic, and non-allergenic. [ABSTRACT FROM AUTHOR]