Ashley Emily C, Fuchs Walter, Klupp Barbara G, Werling Dirk, Graham Simon P, Edwards Jane C
The Pirbright Institute, Ash Road, Woking GU24 0NF, United Kingdom; Centre for Vaccinology and Regenerative Medicine, Department of Pathobiology and Population Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, United Kingdom; School of Biosciences, University of Surrey, Guildford GU2 7XH, United Kingdom.
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Südufer 10, Greifswald - Insel Riems, 17493, Germany.
Vet Immunol Immunopathol. 2025 Jul;285:110960. doi: 10.1016/j.vetimm.2025.110960. Epub 2025 May 29.
Pseudorabies viruses (PrV), the causative agent of Aujeszky's disease, continues to cause economic losses to pig producers across Southeast Asia. PrV is controlled by vaccination with live attenuated vaccines, such as the Bartha K61 strain, which has also shown promise as a viral vector. Despite the success of live attenuated PrV vaccines and their utility to be engineered as vaccine vectors, studies to understand the basis of their immunogenicity are scarce. Here, porcine bone marrow-derived dendritic cells (BMDC) were differentiated by culture with FLT3-L, generating eight myeloid cell populations differing in CADM1, CD172a, CD14, CD163 and CD11c expression, and included CADM1 conventional (c)DC and CD14 DC. In vitro infection of BMDC with GFP-expressing PrV strains Bartha K61 and virulent Kaplan revealed a more rapid infection with Bartha K61. Compared to PrV Kaplan infection, there was also an increase in maturation marker expression (MHC class II and CD80/86) in both infected and bystander BMDC populations following Bartha K61 infection. This was accompanied by a concomitant increased cytokine response. IL-12 and TNF production associated with the cDC and CD14 DC subsets, suggests that infection of these cells may be key to the potent immunogenicity associated with PrV Bartha K61 vaccination.
伪狂犬病病毒(PrV)是奥耶斯基氏病的病原体,持续给东南亚的养猪户造成经济损失。PrV通过接种减毒活疫苗来控制,比如Bartha K61株,该毒株也显示出作为病毒载体的潜力。尽管减毒活PrV疫苗取得了成功,且其作为疫苗载体具有实用性,但了解其免疫原性基础的研究却很匮乏。在这里,猪骨髓来源的树突状细胞(BMDC)通过与FLT3-L共培养进行分化,产生了八个在CADM1、CD172a、CD14、CD163和CD11c表达上存在差异的髓样细胞群体,包括CADM1传统(c)DC和CD14 DC。用表达绿色荧光蛋白的PrV毒株Bartha K61和强毒株Kaplan对BMDC进行体外感染,结果显示Bartha K61的感染速度更快。与PrV Kaplan感染相比,Bartha K61感染后,在感染的和旁观的BMDC群体中,成熟标志物表达(MHC II类分子和CD80/86)也有所增加。这伴随着细胞因子反应的相应增加。与cDC和CD14 DC亚群相关的IL-12和TNF产生,表明这些细胞的感染可能是与PrV Bartha K接种相关的强大免疫原性的关键。