The CD8+ and CD4+ T Cell Immunogen Atlas of Zika Virus Reveals E, NS1 and NS4 Proteins as the Vaccine Targets

Viruses. 2022 Oct 25;14(11):2332. doi: 10.3390/v14112332.

Abstract

Zika virus (ZIKV)-specific T cells are activated by different peptides derived from virus structural and nonstructural proteins, and contributed to the viral clearance or protective immunity. Herein, we have depicted the profile of CD8+ and CD4+ T cell immunogenicity of ZIKV proteins in C57BL/6 (H-2b) and BALB/c (H-2d) mice, and found that featured cellular immunity antigens were variant among different murine alleles. In H-2b mice, the proteins E, NS2, NS3 and NS5 are recognized as immunodominant antigens by CD8+ T cells, while NS4 is dominantly recognized by CD4+ T cells. In contrast, in H-2d mice, NS1 and NS4 are the dominant CD8+ T cell antigen and NS4 as the dominant CD4+ T cell antigen, respectively. Among the synthesized 364 overlapping polypeptides spanning the whole proteome of ZIKV, we mapped 91 and 39 polypeptides which can induce ZIKV-specific T cell responses in H-2b and H-2d mice, respectively. Through the identification of CD8+ T cell epitopes, we found that immunodominant regions E294-302 and NS42351-2360 are hotspots epitopes with a distinct immunodominance hierarchy present in H-2b and H-2d mice, respectively. Our data characterized an overall landscape of the immunogenic spectrum of the ZIKV polyprotein, and provide useful insight into the vaccine development.

Keywords: T cells; Zika virus; epitope; immunodominance; peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Mice
  • Mice, Inbred C57BL
  • Vaccines*
  • Viral Envelope Proteins / immunology
  • Viral Nonstructural Proteins / immunology
  • Zika Virus Infection* / prevention & control
  • Zika Virus*

Substances

  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Vaccines
  • Viral Nonstructural Proteins
  • Viral Envelope Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China (82161148008 and 81971501), Research Units of Adaptive Evolution and Control of Emerging Viruses, Chinese Academy of Medical Sciences (2018RU009), and Excellent Young Scientist Program of the National Natural Science Foundation of China (81822040).