Immunoinformatic approach to design CTL epitope based chimeric vaccine targeting multiple serotypes of dengue virus

Abstract

AbstractThe dengue outbreak is one of the serious global public health concerns. The World Health Organization reported 3,80,171 cases and 113 deaths this year till March 2023, and the rate of infection is expected to increase in vulnerable parts of the world. The development of vaccines is the best approach to managing infectious diseases. All the approved vaccines against dengue are based on live-attenuated virus but they have been questioned for their effectiveness in some population categories. Additionally, random occurrence of four closely related serotypes of dengue virus in humans leading to antibody-dependent enhancement of the disease is yet another cause of vaccine ineffectiveness. Therefore, development of a therapeutic subunit-vaccine based on epitopes from all four serotypes may be expected to provide effective cross-protective cellular immunity. Towards this end, we designed a multi-epitope chimeric immunogen using envelop protein of dengue virus. The MHC-I binding T-cell epitopes were predicted based on their immunogenicity, allergenicity and antigenicity. NetMHCpan-EL4.1 prediction method was used to determine the binding ability of the epitopes with HLA alleles with population coverage of over 99%. The five most potent epitopes based on their immunogenicity, population coverage and prediction scores were selected for each serotype and a multi-epitope polypeptide was generated by merging peptides with AAY linker. The polypeptide was predicted to be an antigen and a non-allergen with a stable tertiary structure retaining a half-life of 4.4 hours in mammalian system. The polypeptide has the potential to elicit effective cellular immune response against all the dengue virus serotypes.