Gómez-Romero Ninnet, Arias Carlos F, Verdugo-Rodríguez Antonio, López Susana, Valenzuela-Moreno Luis Fernando, Cedillo-Peláez Carlos, Basurto-Alcántara Francisco Javier
Vaccinology Laboratory, Department of Microbiology and Immunology, Facultad de Medicina Veterinaria y Zootecnia-Universidad Nacional Autónoma de México, Mexico City, Mexico.
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
Front Vet Sci. 2023 Jun 22;10:1168846. doi: 10.3389/fvets.2023.1168846. eCollection 2023.
Bovine viral diarrhea virus (BVDV) is considered the most important viral pathogen in ruminants worldwide due to the broad range of clinical manifestations displayed by infected animals. Therefore, infection with BVDV leads to severe economic losses in several countries' beef and dairy industries. Vaccination prevents reproductive failure and gastrointestinal and respiratory disorders caused by BVDV infection. However, considering their limitations, conventional vaccines such as live, attenuated, and killed viruses have been applied. Hence, different studies have described subunit vaccines as an effective and safe alternative for BVDV protection. Therefore, in this study, the ectodomain of E2 (E2e) glycoprotein from NADL BVDV strain was expressed in mammalian cells and used in two vaccine formulations to evaluate immunogenicity and protection against BVDV conferred in a murine model. Formulations consisted of solo E2e glycoprotein and E2e glycoprotein emulsified in adjuvant ISA 61 VG. Five groups of 6 mice of 6-to-8-week-old were immunized thrice on days 1, 15, and 30 by intraperitoneal injection with the mentioned formulations and controls. To evaluate the conferred protection against BVDV, mice were challenged six weeks after the third immunization. In addition, the humoral immune response was evaluated after vaccination and challenge. Mice groups inoculated with solo E2e and the E2e + ISA 61 VG displayed neutralizing titers; however, the E2 antibody titers in the E2e + ISA 61 VG group were significantly higher than the mice group immunized with the solo E2e glycoprotein. In addition, immunization using E2e + ISA 61 VG prevents animals from developing severe lesions in surveyed tissues. Moreover, this group acquired protection against the BVDV challenge, evidenced by a significant reduction of positive staining for BVDV antigen in the lungs, liver, and brain between the experimental groups. Our findings demonstrated that using E2e + ISA 61 VG induces greater BVDV protection by an early humoral response and reduced histopathological lesions and BVDV antigen detection in affected organs, indicating that E2e + ISA 61 VG subunit formulation can be considered as a putative vaccine candidate against BVDV. The efficacy and safety of this vaccine candidate in cattle requires further investigation.
牛病毒性腹泻病毒(BVDV)被认为是全球反刍动物中最重要的病毒病原体,因为受感染动物会表现出广泛的临床表现。因此,BVDV感染在多个国家的牛肉和奶牛产业中导致了严重的经济损失。接种疫苗可预防由BVDV感染引起的繁殖失败以及胃肠道和呼吸道疾病。然而,考虑到传统疫苗的局限性,如活病毒疫苗、减毒疫苗和灭活疫苗等已被应用。因此,不同的研究将亚单位疫苗描述为预防BVDV的一种有效且安全的替代方案。因此,在本研究中,NADL BVDV株的E2糖蛋白胞外域(E2e)在哺乳动物细胞中表达,并用于两种疫苗制剂中,以评估其免疫原性以及在小鼠模型中对BVDV的保护作用。制剂包括单独的E2e糖蛋白和在佐剂ISA 61 VG中乳化的E2e糖蛋白。将五组6只6至8周龄的小鼠在第1天、第15天和第30天通过腹腔注射上述制剂和对照进行三次免疫。为了评估对BVDV的保护作用,在第三次免疫后六周对小鼠进行攻毒。此外,在接种疫苗和攻毒后评估体液免疫反应。接种单独E2e和E2e + ISA 61 VG的小鼠组显示出中和效价;然而,E2e + ISA 61 VG组中的E2抗体效价比用单独E2e糖蛋白免疫的小鼠组显著更高。此外,使用E2e + ISA 61 VG进行免疫可防止动物在所检测的组织中出现严重病变。此外,该组获得了针对BVDV攻毒的保护,实验组之间肺、肝和脑中BVDV抗原阳性染色的显著减少证明了这一点。我们的研究结果表明,使用E2e + ISA 61 VG可通过早期体液反应诱导更强的BVDV保护作用,并减少受影响器官中的组织病理学病变和BVDV抗原检测,这表明E2e + ISA 61 VG亚单位制剂可被视为一种潜在的抗BVDV疫苗候选物。这种候选疫苗在牛中的有效性和安全性需要进一步研究。