Department of Medical Clinic, Universidade de São Paulo (USP), Butantã, Brazil.
Department of Animal Production, Universidade Federal de Goiás (UFG), Goiânia, Brazil.
Vet Microbiol. 2024 Sep;296:110155. doi: 10.1016/j.vetmic.2024.110155. Epub 2024 Jul 3.
Bovine Pestivirus typically involves one or more organ systems, with clinical manifestations ranging from mild to severe fatal systemic illness that lead to significant reproductive, productive, and economic losses. Vaccines face the challenge of addressing the significant variability of pestiviruses, which affects the interaction between viral antigens and the immune system's ability to provide protection. This study aimed to evaluate the serological responses against bovine viral diarrhea virus 1 (Pestivirus A) and Pestivirus B induced by 10 commercial vaccines, including one recombinant (vaccine E), two modified live (MLV multivalent, vaccine I, and MLV monovalent, vaccine J), and seven killed vaccines (KLV, vaccines A to H). Additionally, we evaluated the cross-reactivity between Pestivirus A and B from vaccines and HoBi-like pestivirus (Pestivirus H). In Phase 1, guinea pigs were used to screen for non-MLVs. They were divided into nine groups (n=6 each) and received two doses (⅕ of bovine dose) of eight different non-MLV on Days 0 and 21. Serum samples were collected on Days 0 and 30 for serological analyse. In Phase 2, Holstein × Gir heifers (n= 45) were divided into five groups, comprising 6-9 animals. They were vaccinated either once with MLVs or twice with the top non-MLVs screened in Phase 1. Serum samples were harvested on d0 (vaccination day) and d60 (60 days after the first dose) for MLV and non-MLV. Specific antibody titers were assessed virus neutralization (VN) and transformed in log2 for statistical analysis using PROC-MIXED. Significant effects were observed for vaccine groups, time points, and their interactions concerning neutralizing antibodies against Pestivirus A and B in both Guinea pigs and heifers. The Phase 1 study revealed serological responses against Pestivirus A exclusively in non-MLV D (85.33±13.49) and E (72.00±19.26). In the bovine study, the KLD vaccine D (72.00±15.10), recombinant vaccine E (90.66±25.85), and MLV I (170.66±28.22) resulted in an average of neutralizing antibodies against Pestivirus A that exceeded the protective threshold (≥ 60). However,individual analysis of heifers showed a higher frequency of animals presenting titers of Pestivirus A Ab surpassing 32 following vaccination with MLV I and J. None of the vaccine formulations in either study elicited a protective immune response against Pestivirus B or demonstrated cross-reactivity against Pestivirus H.
牛病毒性腹泻病毒通常涉及一个或多个器官系统，临床表现从轻度到严重的致命全身疾病不等，导致严重的生殖、生产和经济损失。疫苗面临着应对瘟病毒显著变异性的挑战，这影响了病毒抗原与免疫系统提供保护能力之间的相互作用。本研究旨在评估 10 种商业疫苗（包括 1 种重组疫苗[疫苗 E]、2 种改良活疫苗[多价 MLV 疫苗 I 和单价 MLV 疫苗 J]和 7 种灭活疫苗[KLV，疫苗 A 至 H]）对牛病毒性腹泻病毒 1（瘟病毒 A）和瘟病毒 B 的血清学反应。此外，我们评估了疫苗中的瘟病毒 A 和 B 与 HoBi 样瘟病毒（瘟病毒 H）之间的交叉反应性。在第 1 阶段，豚鼠用于筛选非 MLV。它们分为 9 组（每组 6 只），在第 0 天和第 21 天接受 8 种不同非 MLV 的两剂（牛剂量的五分之一）。在第 0 天和第 30 天采集血清样本进行血清学分析。在第 2 阶段，荷斯坦 × 吉尔小母牛（n=45）分为 5 组，每组 6-9 只。它们要么用 MLV 单次接种，要么用第 1 阶段筛选出的非 MLV 进行两次接种。在第 0 天（接种日）和第 60 天（第一次剂量后 60 天）采集血清样本用于 MLV 和非 MLV。使用 PROC-MIXED 评估针对 Pestivirus A 和 B 的特异性抗体滴度病毒中和（VN）并转换为 log2 进行统计分析。在豚鼠和小母牛中，疫苗组、时间点及其相互作用对针对 Pestivirus A 和 B 的中和抗体均有显著影响。第 1 阶段的研究仅在非 MLV D（85.33±13.49）和 E（72.00±19.26）中发现了针对 Pestivirus A 的血清学反应。在牛研究中，KLD 疫苗 D（72.00±15.10）、重组疫苗 E（90.66±25.85）和 MLV I（170.66±28.22）导致针对 Pestivirus A 的中和抗体平均超过保护阈值（≥60）。然而，对小母牛的个体分析显示，在接种 MLV I 和 J 后，有更高比例的动物的 Pestivirus A Ab 滴度超过 32。在这两项研究中，没有一种疫苗制剂能产生针对 Pestivirus B 的保护性免疫反应，也没有显示出针对 Pestivirus H 的交叉反应性。
