Animal Disease Biotechnology Laboratory, Department of Animal Science, School of Agriculture, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana.
Animal Diseases Research Unit, USDA-ARS, Pullman, Washington, United States of America.
PLoS One. 2024 Aug 29;19(8):e0306092. doi: 10.1371/journal.pone.0306092. eCollection 2024.
Efficient cattle production and provision of animal-sourced foods in much of Africa is constrained by vector-borne bacterial and protozoal diseases. Effective vaccines are not currently available for most of these infections resulting in a continuous disease burden that limits genetic improvement. We tested whether stimulation of innate immunity using the Toll-like Receptor (TLR) 7 agonist imiquimod, formulated with saponin and water-in-oil emulsion, would protect against morbidity and mortality due to Anaplasma marginale, a tick-borne pathogen of cattle highly endemic in west Africa. In Trial 1, haplotype matched Friesian x Sanga (F1) A. marginale negative calves were allocated to either the experimental group (n = 10) and injected with the synthetic TLR 7 agonist/saponin formulation or to an untreated control group (n = 10). TLR7 agonist/saponin injected calves responded with significantly elevated rectal temperature, enlarged regional lymph nodes, and elevated levels of IL-6 post-injection as compared to control group calves. All calves were then allowed to graze in pasture for natural exposure to tick transmission. All calves in both groups acquired A. marginale, consistent with the high transmission rate in the endemic region. The need for antibiotic treatment, using pre-existing criteria, was significantly lower in the experimental group (odds ratio for not requiring treatment was 9.3, p = 0.03) as compared to the control group. Despite treatment, 6/10 calves in the control group died, reflecting treatment failures that are typical of anaplasmosis in the acute phase, while mortality in the experimental group was 1/10 (odds ratio for survival was 13.5, p = 0.03). The trial was then repeated using 45 Friesian x Sanga calves per group. In Trial 2, the odds ratios for preventing the need for treatment and for mortality in the TLR7 agonist/saponin experimental group versus the control group were 5.6 (p = 0.0002) and 7.0 (p = 0.004), respectively, reproducing the findings of the initial trial. Together these findings demonstrate that innate immune stimulation using a TLR7 agonist formulated with saponin and water-in-oil emulsion provides significant protection against disease caused by tick borne A. marginale in highly susceptible cross-bred cattle, critically important for their potential to increase productivity for smallholder farmers in Africa.
在非洲大部分地区，牛的高效生产和动物源性食品的供应受到媒介传播的细菌和原生动物疾病的限制。目前，大多数这些感染都没有有效的疫苗，这导致了持续的疾病负担，限制了遗传改良。我们测试了使用 Toll 样受体 (TLR) 7 激动剂咪喹莫特刺激先天免疫，与皂苷和水包油乳剂联合使用，是否可以预防在西非高度流行的 tick-borne 病原体边缘无浆体引起的发病率和死亡率。在试验 1 中，匹配 haplotype 的 Friesian x Sanga (F1) 边缘无浆体阴性小牛被分配到实验组 (n = 10) 和接受合成 TLR 7 激动剂/皂苷制剂注射或未治疗对照组 (n = 10)。与对照组小牛相比，TLR7 激动剂/皂苷注射小牛在注射后表现出明显升高的直肠温度、增大的局部淋巴结和升高的 IL-6 水平。然后，所有小牛都被允许在牧场放牧，以自然接触 tick 传播。两组小牛都感染了边缘无浆体，这与流行地区的高传播率一致。使用现有标准，实验组需要抗生素治疗的需求显著降低 (不需要治疗的比值比为 9.3，p = 0.03) 与对照组相比。尽管进行了治疗，但对照组的 6/10 小牛死亡，反映了急性阶段无浆体病的典型治疗失败，而实验组的死亡率为 1/10(存活的比值比为 13.5，p = 0.03)。然后，使用每组 45 头 Friesian x Sanga 小牛重复该试验。在试验 2 中，TLR7 激动剂/皂苷实验组与对照组预防治疗需求的比值比和死亡率分别为 5.6(p = 0.0002) 和 7.0(p = 0.004)，重现了初始试验的结果。这些发现共同表明，使用皂苷和水包油乳剂配制的 TLR7 激动剂刺激先天免疫，为高度易感杂交牛 tick 传播的边缘无浆体引起的疾病提供了显著保护，这对提高非洲小农的生产力具有重要意义。
