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Immunoinformatic based designing of highly immunogenic multi-epitope subunit vaccines to stimulate an adaptive immune response against Junin virus. | LitMetric

AI Article Synopsis

  • - The Junin virus causes Argentine hemorrhagic fever, which can lead to serious symptoms, such as high fever, bleeding, and neurological issues, and can be fatal without timely treatment, with mortality rates up to 30%.
  • - To combat this virus, researchers designed a multi-epitope subunit vaccine using an immunoinformatics approach to identify and validate immunogenic properties of several viral proteins.
  • - The constructed vaccines demonstrated strong binding to human TLR3 and showed promising immune responses in simulations, indicating their potential efficacy in enhancing immune response against the Junin virus.

Article Abstract

The Junin virus causes Argentine hemorrhagic fever, leading to severe complications such as high fever, malaise, muscle pain, and bleeding disorders, including hemorrhages in the skin and mucous membranes. Neurological issues like confusion, seizures, and coma can also occur. Without prompt and effective treatment, the disease can be fatal, with mortality rates reaching up to 30%. Taking serious measures is essential to mitigate the spread of the disease. Vaccination is the most effective choice to neutralize the Junin virus in the current situation. Consequently, to design the highly immunogenic and non-allergenic multi-epitope subunit vaccine against the Junin virus, we employed the immunoinformatic approach to screen the glycoprotein, nucleoprotein, and RDRP protein for potential immunogenic CTL (Cytotoxic T Lymphocyte), HTL (Helper T Lymphocyte) and B (B Lymphocyte) cell epitopes. Afterward, the predicted epitopes were subjected to 3D modeling and validation. The strong binding affinity of the constructed vaccines with the human TLR3 was confirmed through molecular docking, with scores of - 333 kcal/mol for glycoprotein, - 297 kcal/mol for nucleoprotein, - 308 kcal/mol for RDRP, and - 305 kcal/mol for combined vaccines. Additionally, the binding free energies recorded were - 63.54 kcal/mol, - 64.16 kcal/mol, - 56.81 kcal/mol, and - 51.52 kcal/mol, respectively. Furthermore, the dynamic stability, residual fluctuation, and compactness of vaccine-TLR-3 complexes were confirmed by the molecular dynamic simulation. The codon adaptation index (CAI) values and high GC content confirmed the stable expression of constructed vaccines in the pET-28a ( +) expression vector. The immune simulation analysis demonstrated that administering booster doses of the developed vaccines resulted in a notable increase in IgG, IgM, interleukins, and cytokines levels, indicating effective antigen clearance over time. In conclusion, our study provides preclinical evidence for designing a highly effective Junin virus vaccine, necessitating further in-vitro and in-vivo experiments.

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Source
http://dx.doi.org/10.1007/s11030-024-11082-6DOI Listing

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