Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice

Viruses. 2022 Jun 2;14(6):1214. doi: 10.3390/v14061214.

Abstract

Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-γ+ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-γ (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8+ T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.

Keywords: DNA vaccines; cell-mediated immunity; glycoprotein E; herpes zoster; immediate early protein 63.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • CD8-Positive T-Lymphocytes
  • Glycoproteins
  • Herpes Zoster Vaccine*
  • Herpes Zoster*
  • Herpesvirus 3, Human / genetics
  • Immediate-Early Proteins* / genetics
  • Mice
  • Vaccines, DNA*
  • Viral Envelope Proteins / genetics

Substances

  • Antibodies, Viral
  • Glycoproteins
  • Herpes Zoster Vaccine
  • Immediate-Early Proteins
  • Vaccines, DNA
  • Viral Envelope Proteins

Grants and funding

This research was supported by the National Natural Science Foundation of China (grant numbers 32070932 and 31770184) and the Science and Technology Plan Project of the Inner Mongolia Autonomous Region, China (grant number 2020GG0233).