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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Virology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1479794

Development and Immunogenicity Evaluation of a Quadruple-Gene-Deleted Pseudorabies Virus Strain

Provisionally accepted
Hui Li Hui Li 1Riteng Zhang Riteng Zhang 1Jiahao Qu Jiahao Qu 1Yahao Kang Yahao Kang 1Jingnan Zhang Jingnan Zhang 1Ruhai Guo Ruhai Guo 1Junda Li Junda Li 1Xiao Zhang Xiao Zhang 1Likang Han Likang Han 2Honglin Xie Honglin Xie 3Xinglong Wang Xinglong Wang 1*
  • 1 Northwest A&F University, Xianyang, China
  • 2 College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, China
  • 3 Department of Animal Medicine, School of Life Science and Engineering, Foshan University, Foshan, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Since 2011, the emergence of Pseudorabies virus (PRV) variants has led to significant vaccine failures, resulting in severe economic losses in China’s swine industry. Conventional PRV vaccines have shown limited efficacy against these emergent variants, underscoring the urgent need for novel immunization strategies. This study aimed to develop and evaluate a novel recombinant PRV vaccine candidate with improved safety and immunogenicity profiles. Utilizing the homology-directed repair (HDR)-CRISPR/Cas9 system, we generated a recombinant PRV strain, designated PRV SX-10ΔgI/gE/TK/UL24, with deletions in the gI, gE, TK, and UL24 genes. In vitro analyses demonstrated that the recombinant virus exhibited similar replication kinetics and growth curves comparable to the parental strain. The immunological properties of the recombinant PRV were assessed in murine and porcine models. All animals inoculated with PRV SX-10ΔgI/gE/TK/UL24 survived without exhibiting significant clinical signs or pathological alterations. Immunological assays revealed that PRV SX-10ΔgI/gE/TK/UL24 elicited significantly higher levels of gB-specific antibodies, neutralizing antibodies, and cytokines (including IFN-γ, IL-2, and IL-4) compared to both the Bartha-K61 and PRV SX-10ΔgI/gE/TK strains. Notably, both murine and porcine subjects immunized with PRV SX-10ΔgI/gE/TK/UL24 demonstrated enhanced protection against challenges with the variant PRV SX-10 strain, compared to other vaccine strains. These findings suggest that PRV SX-10ΔgI/gE/TK/UL24 represents a promising PRV vaccine candidate strain, offering valuable insights for the prevention and control of PRV in clinical applications.

    Keywords: Pseudorabies virus (PRV), Recombinant vaccine, Gene Deletion, CRISPR/Cas9, Immunogenicity

    Received: 12 Aug 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Li, Zhang, Qu, Kang, Zhang, Guo, Li, Zhang, Han, Xie and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xinglong Wang, Northwest A&F University, Xianyang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.