Designing an mRNA Vaccine against Involved in Fatal Pneumonia Infections via Comparative Proteomics and Reverse Vaccinology Approaches.

Background: is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen.

Methods: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two proteomes, a distinct non-redundant (strain SE8) proteome was chosen. Seven transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity.

Objective: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used.

Results: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1).

Conclusions: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against and it is more suitable for analysis and validation to prove its effectiveness.