Overlapping CD8+ and CD4+ T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach

Abstract

Rift Valley fever virus (RVFV) is an emergent arthropod-borne zoonotic infectious viral pathogen which causes fatal diseases in the humans and ruminants. Currently, no effective and licensed vaccine is available for the prevention of RVFV infection in endemic as well as in non-endemic regions. So, an immunoinformatics-driven genome-wide screening approach was performed for the identification of overlapping CD8+ and CD4+ T-cell epitopes and also linear B-cell epitopes from the conserved sequences of the nucleocapsid (N) and glycoprotein (G) of RVFV. We identified overlapping 99.39% conserved 1 CD8+ T-cell epitope (MMHPSFAGM) from N protein and 100% conserved 7 epitopes (AVFALAPVV, LAVFALAPV, FALAPVVFA, VFALAPVVF, IAMTVLPAL, FFDWFSGLM, and FLLIYLGRT) from G protein and also identified IL-4 and IFN-γ induced (99.39% conserved) 1 N protein CD4+ T-cell epitope (HMMHPSFAGMVDPSL) and 100% conserved 5 G protein CD4+ T-cell epitopes (LPALAVFALAPVVFA, PALAVFALAPVVFAE, GIAMTVLPALAVFAL, GSWNFFDWFSGLMSW, and FFLLIYLGRTGLSKM). The overlapping CD8+ and CD4+ T-cell epitopes were bound with most conserved HLA-C*12:03 and HLA-DRB1*01:01, respectively with the high binding affinity (kcal/mol). The combined population coverage analysis revealed that the allele frequencies of these epitopes are high in endemic and non-endemic regions. Besides, we found 100% conserved and non-allergenic 2 decamer B-cell epitopes, GVCEVGVQAL and RVFNCIDWVH of G protein had the sequence similarity with the nonamer CD8+ T-cell epitopes, VCEVGVQAL and RVFNCIDWV, respectively. Consequently, these epitopes may be used for the development of epitope-based peptide vaccine against emerging RVFV. However, in vivo and in vitro experiments are required for their efficient use as a vaccine.

Keywords: CD4+ T-cell epitope; CD8+ T-cell epitope; Immunoinformatics; Peptide vaccine; Rift Valley fever virus.

Graphical abstract

Fig. 1

Schematic representation of the overall procedures of the vaccine target identification for RVFV nucleocapsid (N) and glycoprotein (G).

Fig. 2

Population coverage by MHC class I and class II restricted epitopes (class combined coverage) predicted from G protein of RVFV. (A) shows maximum coverage by the population of Ireland (Northern) (B) class combined coverage in United States Caucasoid (C) shows population coverage in an endemic country, Sudan (D) represents combined coverage by the overall population of South Asia.

Fig. 3

Docking simulation to predict the binding of predicted and control CD8 + and CD4 + T-cell epitopes to MHC class I (HLA-C*12:03) and MHC class II (HLA-DRB1*01:01) molecule, respectively. The colors, teal cyan and lime green indicate the surface structure of HLA-C*12:03 and HLA-DRB1*01:01, respectively. The red and hot pink colors indicate the CD8 + and CD4 + T-cell epitope, respectively (A) binding of control CD8 + T-cell epitope (GAVDPLLAL) to the binding groove of HLA-C*12:03 (affinity: − 8.4 kcal/mol) (B) represents the binding of control CD4 + T-cell epitope (AGFKGEQGPKGEPG) to the binding groove of HLA-DRB1*01:01 (affinity: − 7.3 kcal/mol) (C) shows the binding affinity of N protein CD8 + T-cell epitope “MMHPSFAGM” to the binding groove of HLA-C*12:03 (affinity: − 7.5 kcal/mol) (D) binding of N protein CD4 + T-cell epitope “HMMHPSFAGMVDPSL” to the binding groove of HLA-DRB1*01:01 (affinity: − 7.0 kcal/mol). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Docking simulation to predict the binding of predicted overlapping G protein CD8 + and CD4 + T-cell epitopes to HLA-C*12:03 and HLA-DRB1*01:01 molecules, respectively. The colors, teal cyan and lime green indicate the surface structure of HLA-C*12:03 and HLA-DRB1*01:01, respectively. The red and hot pink colors indicate the CD8 + and CD4 + T-cell epitope, respectively. The binding of CD8 + T-cell epitopes to the binding groove of MHC class I allele HLA-C*12:03 (A) “AVFALAPVV” (affinity: − 8.8 kcal/mol) (B) “LAVFALAPV” (affinity: − 9.1 kcal/mol) (C) “FALAPVVFA” (affinity: − 7.9 kcal/mol) and (D) “VFALAPVVF” (affinity: − 9.0 kcal/mol). On the other hand, the binding of CD4 + T-cell epitopes to the binding groove of MHC class II allele HLA-DRB1*01:01 (E) “LPALAVFALAPVVFA” (affinity: − 7.6 kcal/mol) (F) “PALAVFALAPVVFAE” (affinity: − 9.0 kcal/mol). These 2 CD4 + T-cell epitopes overlapped with the above mentioned 4 CD8 + T-cell epitopes. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Docking simulation to predict the binding of predicted overlapping G protein CD8 + and CD4 + T-cell epitopes to HLA-C*12:03 and HLA-DRB1*01:01 molecules, respectively. The colors, teal cyan and lime green indicate the surface structure of HLA-C*12:03 and HLA-DRB1*01:01, respectively. The red and hot pink colors indicate the CD8 + and CD4 + T-cell epitope, respectively. (A) CD8 + T-cell epitope “IAMTVLPAL” (affinity: − 8.5 kcal/mol) (B) CD4 + T-cell epitope “GIAMTVLPALAVFAL” (affinity: − 7.6 kcal/mol) (C) CD8 + T-cell epitope “FFDWFSGLM” (affinity: − 8.5 kcal/mol) (D) CD4 + T-cell epitope “GSWNFFDWFSGLMSW” (affinity: − 9.0 kcal/mol) (E) CD8 + T-cell epitope “FLLIYLGRT” (affinity: − 8.7 kcal/mol) and (F) CD4 + T-cell epitope “FFLLIYLGRTGLSKM” (affinity: − 6.5 kcal/mol). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)