CRM197-conjugated peptides vaccine of HCMV pp65 and gH induce maturation of DC and effective viral-specific T cell responses

Virulence. 2023 Dec;14(1):2169488. doi: 10.1080/21505594.2023.2169488.

Abstract

Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

Keywords: Human cytomegalovirus; T cell immunity; antigen presentation; maturation of DCs; peptide-CRM197 vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus Vaccines*
  • Cytomegalovirus* / genetics
  • Glycoproteins
  • Humans
  • Peptides
  • T-Lymphocytes

Substances

  • CRM197 (non-toxic variant of diphtheria toxin)
  • Cytomegalovirus Vaccines
  • Glycoproteins
  • Peptides
  • cytomegalovirus matrix protein 65kDa

Grants and funding

The work was supported by the National Science and Technology Program during the Twelfth Five-year Plan Period [2018YFA0900802]; Qingdao Municipal Science and technology Foundation [20-2-3-4-nsh]; Shandong Provincial Science and technology Foundation [no. 2019JZZY011009].