Exploring dengue genome to design effective multi epitope-based peptide vaccine by immunoinformatics approach against all serotypes of dengue virus

Abstract

Dengue fever is an acute tropical disease that is spread by Aedes species mosquitoes. It is a virus-mediated illness that causes headaches, fever, severe joint and muscle pain, swollen glands (lymphadenopathy), and rashes. Every year, 390 million people around the world suffer from it and ∼20 % die from cases that are left untreated. The virus is transmitted to humans by mosquito bites of infected Aedes species. When it gets into the body, its envelope protein attaches to the host cell surface receptor and initiates the viral infection cycle by the formation of a smooth coat with icosahedral symmetry. Due to its high mutation-prone nature and differences in protein sequences among serotypes, it is difficult to develop a stable vaccine suitable against all serotypes. In this study, a software-based vaccinology approach was used to design a vaccine construct against the envelope protein of all four subtypes of the dengue virus. This construct was designed by joining two epitopes of the protein. One epitope was taken from the envelope protein of DEN-2 which was conserved for DEN-1, DEN-2, and DEN-3, and another epitope from the same protein of DEN-4 serotype as the sequence composition of the protein is slightly different in these two groups of serotypes. Here, firstly 18 epitopes for dengue virus-1, 2, 3, and 12 epitopes for dengue virus-4 were retrieved based on the highest combined score of NetCTL server analysis of human leukocyte antigen (HLA) supertypes. Among them, the epitope MAILGDTAW has shown 100 % conservancy in strains of dengue virus 1, 2, 3, and KLRIKGMSY, TTAKEVALL, TPRSPSVEV, FRKGSSIGK, KTWLVHKQW have shown 100 % conservancy in dengue virus 4. In population coverage analysis, MAILGDTAW has shown 88.63 % and FRKGSSIGK has shown 90.72 % (highest among other DEN-4 epitopes) population coverage of the entire world population. These two epitopes along with their 15-mer extensions (MHCII binding peptides) were found as non-allergen and non-toxic. Finally, the two different 15-mer extensions (to get 100 % sequence conservancy) of the epitope MAILGDTAW and the 15-mer extension of the epitope FRKGSSIGK were put together using an EAAAK linker to construct the multi-epitope vaccine. In-vivo analysis of the proposed vaccine construct would aid in the development of a functional immune response that would eradicate dengue complications worldwide.