Azim, K. F. | Search bioRxiv

bioRxiv2018

Vaccinomics strategy for developing a unique multi-epitope monovalent vaccine against Marburg marburgvirus

Marburg virus causes severe hemorrhagic fever in both humans and non-human primates with high degree of infectivity and lethality. To date no approved treatment is available for Marburg virus infection. A study was employed to design a novel chimeric vaccine against Marburg virus by adopting reverse vaccinology approach. Envelope glycoprotein and matrix protein VP40 were identified as most antigenic viral proteins which generated a plethora of antigenic epitopes. Results showed that vaccine construct V1 was superior in terms of various physicochemical properties and structural stability. Molecular docking analysis of the refined vaccine with different MHCs and human immune TLR8 receptor demonstrated higher binding affinity. Moreover, complexed structure of the modeled vaccine and TLR8 indicated minimal deformability at molecular level. Translational potency and microbial expression of the modeled vaccine within E. coli strain K12 by pET28a(+) vector were also biologically significant. However, further in vitro and in vivo investigation could be implemented for the acceptance and validation of the designed vaccine against Marburg virus.

bioinformatics↗

bioRxiv2018

Reverse vaccinology approach to design a novel multi-epitope subunit vaccine against avian influenza A (H7N9) virus

H7N9, a novel strain of avian origin influenza was the first recorded incidence where a human was transited by a N9 type influenza virus. Effective vaccination against influenza A (H7N9) is a major concern, since it has emerged as a life threatening viral pathogen. Here, an in silico reverse vaccinology strategy was adopted to design a unique chimeric subunit vaccine against avian influenza A (H7N9). Induction of humoral and cell-mediated immunity is the prime concerned characteristics for a peptide vaccine candidate, hence both T cell and B cell immunity of viral proteins were screened. Antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach were adopted to generate the most antigenic epitopes of avian influenza A (H7N9) proteome. Further, a novel subunit vaccine was designed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. Physicochemical properties and secondary structure of the designed vaccine were assessed to ensure its thermostability, hydrophilicity, theoretical PI and structural behavior. Homology modeling, refinement and validation of the designed vaccine allowed to construct a three dimensional structure of the predicted vaccine, further employed to molecular docking analysis with different MHC molecules and human immune TLR8 receptor present on lymphocyte cells. Moreover, disulfide engineering was employed to lessen the high mobility region of the designed vaccine in order to extend its stability. Furthermore, we investigated the molecular dynamic simulation of the modeled subunit vaccine and TLR8 complexed molecule to strengthen our prediction. Finally, the suggested vaccine was reverse transcribed and adapted for E. coli strain K12 prior to insertion within pET28a(+) vector for checking translational potency and microbial expression.

bioinformatics↗