Novel Multi-Epitope Vaccine candidate derived from critically important proteins of Monkeypox isolates

Abstract

BackgroundOn May 7, 2022, a case of monkeypox virus (MPXV) has been reported to the WHO. It causes a viral zoonotic disease with characteristics comparable to that of smallpox cases. Monkeypox could be a serious health concern as it is already spreading to multiple countries worldwide. To prevent the monkeypox infection and for its early detection, a potential vaccine and diagnostic candidate is urgently required. MethodIn present study we have used different in silico methods to screen the entire genome with its approximately 191 genes for potential epitopes present in proliferation and virulent proteins of monkeypox virus. All protein sequences were retrieved from different genomic and proteome databases listed in Uniprot or NCBI. ResultsIn the present study we have screened potential epitopes from 11 different proteins of Monkeypox. All the included protein play an important role in pathogenesis and/or proliferation of Monkeypox virus. We have identified in total 984 CTL and 168 HTL epitopes with highest score in our epitope screening. The reported epitopes could be potential candidates for the design of an early detection diagnostic kit specific for the monkeypox virus. Out of these target peptides we have included a total of 39 CTL epitopes and 39 HTL epitopes in design of multi-epitope vaccine candidates. These shortlisted epitopes are highly conserved amongst different strains and origin of monkeypox viruses. The population coverage by joint administration of CTL and HTL MEVs is predicted to be high with the epitopes showing potential to bind upto 24 different CTL and HTL HLA allele molecules. The epitopes used in MEVs are examined to be highly immunogenic, non allergic but antigenic, and non toxic. All the CTL and HTL MEVs designed utilizing the epitopes have physiochemical properties favor its over expression in human cells. The optimized cDNA constructs of CTL and HTL MEVs also favor over expression of MEVs in human cells. Overall, the MEV construct proposed by us are fissile for expression in the lab and for further in vivo studies. ConclusionControl and fight against emerging diseases such as MPXV requires pathogen diagnostic and novel vaccine approaches. We screened for several epitopes and designed a MEV providing a potential solution for both purposes. Our method allows rapid screening and provides a rational strategy for the development of vaccine candidate effective in fighting MPXV and other unexpected upcoming diseases.