Animal Disease Research Unit, United States Department of Agricultural - Agricultural Research Service, Pullman, WA, United States.
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United States.
Front Immunol. 2023 Jul 31;14:1219913. doi: 10.3389/fimmu.2023.1219913. eCollection 2023.
Live attenuated vaccines produced by sequential passages in splenectomized calves have historically been used to control acute bovine babesiosis in endemic areas worldwide. However, several constraints prevent the widespread use of these vaccines, including the need for several splenectomized calves to produce vaccine batches, and potential inconsistent parasite attenuation, which contraindicates their use for highly -susceptible adult cattle. Thus, the use of vaccines based on well-defined culture attenuated strains emerges as a more sustainable and efficient alternative. Previous work demonstrated that the culture attenuated strain Att-S74-T3Bo is non-tick transmissible and able to safely protect calves against needle challenge with a virulent strain.
Herein we evaluated safety and efficacy of Att-S74-T3Bo in preventing acute babesiosis in adult (>1.5 year of age) cattle. Results demonstrated that Att-S74-T3Bo vaccination of adult animals (n=5) induced self-limiting signs of acute infection and protected the vaccinated animals against challenge with the homologous virulent strain Vir-S74-T3Bo. Att-S74-T3Bo-vaccinated adult cattle developed significant (P<0.05) monocytosis, with concomitant neutropenia and CD4 leukopenia, in peripheral blood early after vaccination. Also, vaccinated animals developed a specific signature of pro- and anti-inflammatory cytokine expression in peripheral blood and significant levels of IgM, total IgG, IgG1, and IgG2 against the immunodominant antigen RAP-1 CT. Strikingly, none of the vaccinated animals showed any signs of acute babesiosis after challenge with Vir-S74-T3Bo. In contrast, control adult cattle (n=5) showed pathognomonic symptoms of acute babesiosis, and significant decrease (P<0.05) in lymphocytes, monocytes, and neutrophils, starting on day 7 post-challenge. All control animals developed severe acute disease and were euthanized on days 10 through 12 days post-challenge.
Evidence from this study indicates that Att-S74-T3Bo safely protects highly susceptible adult cattle against challenge with a homologous virulent strain of . In conclusion, Att-S74-T3Bo may be considered as a potential efficient and sustainable attenuated candidate vaccine strain to control acute bovine babesiosis in highly susceptible adult cattle. Future studies should focus on increasing the number of animals vaccinated, duration of immunity, and efficacy of this attenuated strain against heterologous virulent parasite strains.
通过在脾切除小牛中连续传代生产的活减毒疫苗,在历史上一直被用于控制全球流行地区的急性牛巴贝斯虫病。然而,有几个限制因素阻止了这些疫苗的广泛使用,包括需要几只脾切除小牛来生产疫苗批次,以及寄生虫减毒的潜在不一致性,这使得它们不能用于高度易感的成年牛。因此,使用基于明确培养减毒株的疫苗成为一种更可持续和有效的替代方法。先前的工作表明,培养减毒株 Att-S74-T3Bo 是非蜱传的,能够安全地保护小牛免受同源强毒力菌株的针状挑战。
本文评估了 Att-S74-T3Bo 在预防成年(>1.5 岁)牛急性巴贝斯虫病中的安全性和有效性。结果表明,Att-S74-T3Bo 疫苗接种成年动物(n=5)诱导了急性感染的自限性体征,并保护接种动物免受同源强毒力菌株 Vir-S74-T3Bo 的攻击。Att-S74-T3Bo 疫苗接种的成年牛在早期外周血中出现显著的(P<0.05)单核细胞增多症,同时伴有中性粒细胞减少和 CD4 白细胞减少。此外,接种动物在外周血中产生了促炎和抗炎细胞因子表达的特定特征,并产生了针对免疫优势抗原 RAP-1 CT 的特异性 IgM、总 IgG、IgG1 和 IgG2。值得注意的是,在接受 Vir-S74-T3Bo 挑战后,没有一只接种动物表现出任何急性巴贝斯虫病的迹象。相比之下,对照组成年牛(n=5)表现出急性巴贝斯虫病的特征性症状,并且在挑战后第 7 天开始,淋巴细胞、单核细胞和中性粒细胞显著减少(P<0.05)。所有对照动物均发展为严重的急性疾病,并在挑战后第 10 至 12 天被安乐死。
本研究的证据表明,Att-S74-T3Bo 可安全地保护高度易感的成年牛免受同源强毒力菌株的挑战。总之,Att-S74-T3Bo 可被视为一种有潜力的高效和可持续的减毒候选疫苗株,用于控制高度易感的成年牛的急性牛巴贝斯虫病。未来的研究应侧重于增加接种动物的数量、免疫持续时间以及该减毒株对异源强毒寄生虫株的疗效。