Recombinant Pseudorabies Virus with TK/gE Gene Deletion and Flt3L Co-Expression Enhances the Innate and Adaptive Immune Response via Activating Dendritic Cells

Viruses

Hao Wu¹  Qigai He¹  Qi Sun¹  Siqi Chen¹  Lun Yao¹  Xuexiang Yu¹  Qiao Hu¹  Tong Zhou¹  Ahmed. H. Ghonaim¹  Hailong Ma¹  Shengxian Fan¹ 

[1] State Key Laboratory of Agricultural Microbiology College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China;

关键词: emerging PRV;    dendritic cells;    vaccine;    immune response;   

DOI  :  10.3390/v13040691

来源: DOAJ

【 摘 要 】

Owing to viral evolution and recombination, emerging pseudorabies virus (PRV) strains have caused unprecedented outbreaks in swine farms even when the pigs were previously vaccinated, which might indicate that traditional vaccines were unable to provide effective protection. The development of safe and efficacious vaccines presents prospects to minimize the clinical signs and eventually eradicate the infection. In this study, we used an emerging PRV strain, HNX, as the parental strain to construct a recombinant PRV with TK/gE gene deletion and Fms-related tyrosine kinase 3 ligand (Flt3L) expression, named HNX-TK⁻/gE⁻-Flt3L. HNX-TK⁻/gE⁻-Flt3L enhanced the maturation of bone marrow derived dendritic cells (DCs) in vitro. Significantly more activated DCs were detected in HNX-TK⁻/gE⁻-Flt3L-immunized mice compared with those immunized with HNX-TK⁻/gE⁻. Subsequently, a remarkable increase of neutralizing antibodies, gB-specific IgG antibodies, and interferon-gamma (IFN-γ) was observed in mice vaccinated with HNX-TK⁻/gE⁻-Flt3L. In addition, a lower mortality and less histopathological damage were observed in HNX-TK⁻/gE⁻-Flt3L vaccinated mice with upon PRV lethal challenge infection. Taken together, our results revealed the potential of Flt3L as an ideal adjuvant that can activate DCs and enhance protective immune responses and support the further evaluation of HNX-TK⁻/gE⁻-Flt3L as a promising PRV vaccine candidate.

【 授权许可】

Unknown