Designing a multi-epitope universal vaccine for concurrent infections of SARS-CoV-2 and influenza viruses using an immunoinformatics approach.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and influenza viruses share several conserved epitopes that can be utilized for the development of universal vaccines. Our previous research demonstrated that recombinant M2e-HA2 (Matrix-2 ectodomain-Hemagglutinin subunit 2) proteins derived from influenza elicited an immune response against the virus, suggesting their potential use in universal influenza vaccine formulations. Given the lack of a specific vaccine to address SARS‑CoV‑2 and influenza co-infections, this study aimed to design a universal vaccine using immunoinformatics methodologies.

Methods: In this study, B-cell and T-cell epitopes were identified from the nucleocapsid (N) protein of SARS‑CoV‑2. Additionally, the N-terminal segments of M2e (SLLTEVET) and HA2 (GLFGAIAGF) from influenza were incorporated to construct a multi-epitope vaccine. Suitable linkers were designed, and human beta-defensin-2 was selected as an adjuvant. Further evaluations were conducted, focusing on key parameters such as stability, allergenicity, and antigenicity.

Results: The major histocompatibility complex (MHC) class I and II binding epitopes exhibited broad population coverage for the vaccine on a global scale. The vaccine structure was found to interact with toll-like receptor 3 (TLR-3), and the docked conformation of the vaccine/TLR-3 complex demonstrated high stability during molecular dynamics (MD) simulations. The constructed vaccine exhibited thermal stability across cold, ambient, and human body temperatures. Additionally, in silico cloning of the vaccine candidate into the pET-28a(+) vector was performed to facilitate production within the Escherichia coli expression system.

Conclusion: Overall, the findings suggest that the designed vaccine has the potential to serve as an effective universal vaccine and a promising strategy for controlling both Coronavirus disease 2019 (COVID-19) and influenza on a global scale.