Designing a T cell multi-epitope vaccine against hRSV with reverse vaccinology: An immunoinformatics approach

As an infectious viral pathogen, human respiratory syncytial virus (hRSV) can cause severe respiratory infections and is recognized as one of the highest priority pathogens by the World Health Organization (WHO). Although vaccines play an important role in disease prevention and transmission, the wild-type virus is usually prone to immune escape due to the relatively high mutation rate of biological proteins. Therefore, designing a broad-spectrum hRSV vaccine is essential to provide extensive protection against multiple viral variants. Using a consensus sequence approach, we designed a broad-spectrum T-cell epitope vaccine composed of 385 amino acids, consisting of 12 CTLs and 5 HTLs from the fusion protein and glycoprotein. The designed multi-epitope vaccine was expected to have non-allergenicity, high population coverage, strong antigenicity and immunogenicity, appropriate physical and chemical properties, and high solubility. Meanwhile, the structure of the vaccine had a high similarity to that of the natural virus. In addition, through structural biology analysis, the constructed vaccine achieved robust structural compactness and binding stability. Computer-generated immunological simulations indicated that the vaccine could elicit realistic immune responses in humans. The designed vaccine showed good binding affinity and molecular and immune simulation. In conclusion, the broad-spectrum hRSV vaccine could be an excellent candidate for preventing hRSV infection. The employed prediction pipeline was proved to be an efficient method for screening immunogenic epitopes of additional pathogens.