Development of a BoHV-4 viral vector expressing tgD of BoHV-1 and evaluation of its immunogenicity in mouse model

Braz J Microbiol. 2021 Sep;52(3):1119-1133. doi: 10.1007/s42770-021-00525-z. Epub 2021 Jul 13.

Abstract

In recent years, Bovine herpesvirus 4 (BoHV-4) has emerged as an attractive gene delivery viral vector, mainly for vaccination purposes in the veterinary field. In the present study, a new infectious clone of the BoHV-4 genome carrying a bacterial artificial chromosome vector (BoHV-4-BAC) was developed by homologous recombination in mammalian cell culture and bacterial systems, and exploited to express a truncated form of glycoprotein D (tgD) of Bovine herpesvirus 1 (BoHV-1) (BoHV-4-tgD∆TK) as a vaccine candidate. This construct's immunogenicity was compared to a DNA vector expressing the same antigen (pC-tgD) in a BALB/c mouse model. After the mice were immunized, total and specific antibody responses, cytokine responses, total splenocyte cells proliferation/cytotoxicity, and virus neutralization assays were conducted to analyze the immune response elicited by both constructs. Mice from both vaccine groups developed significant humoral and cellular immune responses after a booster dose regime was conducted on day 28 post-injection. In almost all immunological assays, BoHV-4-tgDΔTK induced as high an immune response as pC-tgD. In both vaccine constructs, neutralizing antibodies were a significant determining factor in protection against BoHV-1, even after the first injection. We conclude that a BoHV-4-based viral vector offers an effective immunization strategy as an alternative to DNA-based immunization platforms, at least to combat BoHV-1.

Keywords: Bovine herpesvirus 1; Bovine herpesvirus 4; Immune response; TgD; Viral vector.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Herpesvirus 1, Bovine* / genetics
  • Herpesvirus 1, Bovine* / immunology
  • Herpesvirus 4, Bovine* / genetics
  • Mice
  • Mice, Inbred BALB C
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Proteins
  • bovine herpesvirus type-1 glycoproteins