An Immunoinformatics Approach to Design a Potent Multi-Epitope Vaccine against Asia-1 Genotype of Crimean-Congo Haemorrhagic Fever Virus Using the Structural Glycoproteins as a Target.

Crimean-Congo haemorrhagic fever (CCHF), caused by Crimean-Congo haemorrhagic fever virus (CCHFV), is a disease of worldwide importance (endemic yet not limited to Asia, Middle East, and Africa) and has triggered several outbreaks amounting to a case fatality rate of 10-40% as per the World Health Organization. Genetic diversity and phylogenetic data revealed that the Asia-1 genotype of CCHFV remained dominant in Pakistan, where 688 confirmed cases were reported between the 2012-2022 period. Currently, no approved vaccine is available to tackle the viral infection. Epitope-based vaccine design has gained significant attention in recent years due to its safety, timeliness, and cost efficiency compared to conventional vaccines. In the present study, we employed a robust immunoinformatics-based approach targeting the structural glycoproteins G1 and G2 of CCHFV (Asia-1 genotype) to design a multi-epitope vaccine construct. Five B-cells and six cytotoxic T-lymphocytes (CTL) epitopes were mapped and finalized from G1 and G2 and were fused with suitable linkers (EAAAK, GGGS, AAY, and GPGPG), a PADRE sequence (13 aa), and an adjuvant (50S ribosomal protein L7/L12) to formulate a chimeric vaccine construct. The selected CTL epitopes showed high affinity and stable binding with the binding groove of common human HLA class I molecules (HLA-A*02:01 and HLA-B*44:02) and mouse major histocompatibility complex class I molecules. The chimeric vaccine was predicted to be an antigenic, non-allergenic, and soluble molecule with a suitable physicochemical profile. Molecular docking and molecular dynamics simulation indicated a stable and energetically favourable interaction between the constructed antigen and Toll-like receptors (TLR2, TLR3, and TLR4). Our results demonstrated that innate, adaptive, and humoral immune responses could be elicited upon administration of such a potent muti-epitope vaccine construct. These results could be helpful for an experimental vaccinologist to develop an effective vaccine against the Asia-1 genotype of CCHFV.

Advances In Research On Genome Editing Crispr-Cas9 Technology.

BACKGROUND: The current era of genome engineering has been revolutionized by the evolution of a bacterial adaptive immune system, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) into a radical technology that is making an expeditious progress in its mechanism, function and applicability.. METHODS: A systematic literature review study was carried out with the help of all available information and online resources.. RESULTS: In this review, we intend to elucidate different aspects of CRISPR in the light of current advancements. Utilizing a nonspecific Cas9 nuclease and a sequence specific programmable CRISPR RNA (crRNA), this system cleaves the target DNA with high precision. With a vast potential for profound implications, CRISPR has emerged as a mainstream method for plausible genomic manipulations in a range of organisms owing to its simplicity, accuracy and speed. A modified form of CRISPR system, known as CRISPR/Cpf1 that employs a smaller and simpler endonuclease (Cpf1) than Cas9, can be used to overcome certain limitations of CRISPR/Cas9 system. Despite clear-cut innovative biological applications, this technology is challenged by off-target effects and associated risks, thus safe and controlled implementation is needed to enable this emerging technique assist both biological research and translational applications. CONCLUSIONS: CRISPR/Cas9 systems will undoubtedly revolutionize the study and treatment of both immunologic and allergic diseases. Concerned authorities should formulate and authorize such laws and regulations that permit the safe and ethical use of this emerging technology for basic research and clinical purposes.

Antigenic Peptide Prediction From E6 and E7 Oncoproteins of HPV Types 16 and 18 for Therapeutic Vaccine Design Using Immunoinformatics and MD Simulation Analysis.

Human papillomavirus (HPV) induced cervical cancer is the second most common cause of death, after breast cancer, in females. Three prophylactic vaccines by Merck Sharp & Dohme (MSD) and GlaxoSmithKline (GSK) have been confirmed to prevent high-risk HPV strains but these vaccines have been shown to be effective only in girls who have not been exposed to HPV previously. The constitutively expressed HPV oncoproteins E6 and E7 are usually used as target antigens for HPV therapeutic vaccines. These early (E) proteins are involved, for example, in maintaining the malignant phenotype of the cells. In this study, we predicted antigenic peptides of HPV types 16 and 18, encoded by E6 and E7 genes, using an immunoinformatics approach. To further evaluate the immunogenic potential of the predicted peptides, we studied their ability to bind to class I major histocompatibility complex (MHC-I) molecules in a computational docking study that was supported by molecular dynamics (MD) simulations and estimation of the free energies of binding of the peptides at the MHC-I binding cleft. Some of the predicted peptides exhibited comparable binding free energies and/or pattern of binding to experimentally verified MHC-I-binding epitopes that we used as references in MD simulations. Such peptides with good predicted affinity may serve as candidate epitopes for the development of therapeutic HPV peptide vaccines.

"Why we could not eradicate polio from pakistan and how can we?"

Polio is a major health problem and a deadly infectious disease in the developing countries. It is a viral illness caused by polio virus that can lead to paralysis, limb deformities, breathing problems or even death. Polio virus resides only in humans and passes on to the environment in the faeces of someone who is infected. Polio is still endemic in three countries, i.e., Pakistan, Nigeria and Afghanistan and is eradicated from the rest of the world. Pakistan is considered as the exporter of Wild Polio Virus (WPV) with highest number of polio outbreaks among endemic countries. With the start of World Polio Eradication Initiative in 1988, the number of polio cases has been reduced up to 99% worldwide until now. In 2015, Pakistan has shown a decrease of 70-75% in number of polio cases as compare to last year which is the result of good government's initiatives. Militant organizations such as Tehreek-e-Taliban Pakistan, Al-Qaeda and Boko haram movement of northern Nigeria are a major hurdle in the eradication of polio from these countries. The misconception of people about polio vaccine, insecurity within the country and poor health system are the reasons of failure of polio eradication campaigns in these regions. Awareness campaigns about polio for locals and development of proper health system will help in the eradication of polio. Once polio is eradicated, about 40-50 billion dollars can be saved globally. With the strong commitment, seriousness and good initiatives, polio will be eradicated from Pakistan within two years more likely.