A recombinant pseudorabies virus surface - displaying the classical swine fever E2 protein induces specific antibodies rapidly

Vet Microbiol. 2024 Nov:298:110240. doi: 10.1016/j.vetmic.2024.110240. Epub 2024 Sep 5.

Abstract

Pseudorabies virus (PRV) and classical swine fever virus (CSFV) are both economically important pathogens threatening the pig industry in many countries. The triple-gene-deleted variant of PRV, herein referred to as rPRVTJ-delgE/gI/TK, has exhibited pronounced efficacy and safety profiles. This underscores its viability as a prospective vaccine vector. However, the generation of specific anti-E2 antibodies necessitates elevated immunization doses and extended durations when the extracellular domain of the E2 protein of CSFV is secreted via the recombinant rPRVTJ-delgE/gI/TK vector. To enhance the presentation of exogenous antigens by antigen-presenting cells (APCs), we engineered the E2 protein expressed on the surface of PRV particles in this study. The recombinant virus expressing the E2 protein with a heterogonous transmembrane domain was generated in the backbone of rPRVTJ-delgE/gI/TK and designated as rPRVTJ-UL44-E2. The E2 gene was fused to the 3' terminus of the UL44 gene utilizing P2A, a self-cleaving peptide sequence. The electron microscopy showed that the E2 protein was anchored on the surface of the viral particles of rPRVTJ-delgE/gI/TK-E2. The insertion of the E2 gene did not alter the native biological characteristics of the viral vector. Rabbits immunized with 107 median tissue culture infective doses (TCID50) of rPRVTJ-UL44-E2 exhibited a rapid seroconversion to anti-E2 specific antibodies within 7 days post-immunization (dpi). All the rabbits immunized with the rPRVTJ-UL44-E2 had generated antibodies specific to E2 prior to the administration of the booster immunization. However, the immunized rabbits were not protected from the CSFV C-strain challenge. Nevertheless, this strategy has notably achieved rapid induction of E2-specific non-neutralizing antibodies. These findings provide insights that the design of rPRVTJ-UL44-E2 requires optimization, thereby indicating a promising avenue for augmenting vaccine-induced immune responses.

Keywords: Classical swine fever virus; E2 protein; Immunogenicity; Pseudorabies virus; UL44.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Classical Swine Fever / immunology
  • Classical Swine Fever / prevention & control
  • Classical Swine Fever / virology
  • Classical Swine Fever Virus* / genetics
  • Classical Swine Fever Virus* / immunology
  • Herpesvirus 1, Suid* / genetics
  • Herpesvirus 1, Suid* / immunology
  • Pseudorabies / immunology
  • Pseudorabies / prevention & control
  • Pseudorabies / virology
  • Rabbits
  • Swine
  • Viral Envelope Proteins* / genetics
  • Viral Envelope Proteins* / immunology
  • Viral Vaccines / immunology

Substances

  • Antibodies, Viral
  • Viral Envelope Proteins
  • glycoprotein E2, classical swine fever virus
  • Viral Vaccines
  • Antibodies, Neutralizing