Infectious Bacterial Diseases, National Animal Disease Center, Agriculture Research Service, USDA, Ames, Iowa, USA
Infectious Bacterial Diseases, National Animal Disease Center, Agriculture Research Service, USDA, Ames, Iowa, USA.
mSphere. 2021 Mar 24;6(2):e00988-20. doi: 10.1128/mSphere.00988-20.
This study examined the humoral and cellular response of cattle vaccinated with two commercial leptospiral vaccines, Leptavoid and Spirovac, and a novel bacterin vaccine using Seppic Montanide oil emulsion adjuvant. Vaccination was followed by experimental challenge. All vaccinated cattle were protected from colonization of the kidney and shedding of in urine, as detected by culture and immunofluorescence assay. Agglutinating antibody titers were detected in vaccinated cattle at 4 weeks following vaccination, with small anamnestic response detected following experimental challenge. Only animals vaccinated with the oil emulsion-adjuvanted bacterin produced significant IgG2 titers following vaccination, and nonvaccinated animals produced serum IgA titers after experimental challenge. CD4 and γδ T cells from vaccinated cattle proliferated when cultured with antigen Cellular responses included a marked proliferation of γδ T cells immediately following experimental challenge in vaccinated cattle and release of gamma interferon (IFN-γ), interleukin 17a (IL-17a), and IL-12p40 from stimulated cells. Proliferative and cytokine responses were found not just in peripheral mononuclear cells but also in lymphocytes isolated from renal lymph nodes at 10 weeks following experimental challenge. Overall, effects of leptospirosis vaccination and infection were subtle, resulting in only modest activation of CD4 and γδ T cells. The use of Seppic Montanide oil emulsion adjuvants may shorten the initiation of response to vaccination, which could be useful during outbreaks or in areas where leptospirosis is endemic. Leptospirosis is an underdiagnosed, underreported zoonotic disease of which domestic livestock can be carriers. As a reservoir host for serovar Hardjo, cattle may present with reproductive issues, including abortion, birth of weak or infected calves, or failure to breed. Despite years of study and the availability of commercial vaccines, detailed analysis of the bovine immune response to vaccination and challenge is lacking. This study evaluated immunologic responses to two efficacious commercial vaccines and a novel bacterin vaccine using an adjuvant chosen for enhanced cellular immune responses. Antigen-specific responsive CD4 and γδ T cells were detected following vaccination and were associated with release of inflammatory cytokines IFN-γ and IL-17a after stimulation. CD4 and γδ cells increased in the first week after infection and, combined with serum antibody, may play a role in clearance of bacteria from the blood and resident tissues. Additionally, these antigen-reactive T cells were found in the regional lymph nodes following infection, indicating that memory responses may not be circulating but are still present in regional lymph nodes. The information gained in this study expands knowledge of bovine immune response to leptospirosis vaccines and infection. The use of oil emulsion adjuvants may enhance early immune responses to leptospiral bacterins, which could be useful in outbreaks or situations where leptospirosis is endemic.
本研究考察了两种商业钩端螺旋体疫苗(Leptavoid 和 Spirovac)和一种使用 Seppic Montanide 油乳剂佐剂的新型菌苗对牛的体液和细胞反应。接种后进行了实验性攻毒。所有接种疫苗的牛均未被定植于肾脏,也未通过培养和免疫荧光检测到尿液中 的排出。接种后 4 周,接种牛可检测到凝集抗体滴度,实验性攻毒后可检测到小的回忆反应。只有接种油乳剂佐剂菌苗的动物在接种后产生了显著的 IgG2 滴度,而非接种动物在实验性攻毒后产生了血清 IgA 滴度。接种牛的 CD4 和 γδ T 细胞在培养时与抗原一起增殖。细胞反应包括接种牛在实验性攻毒后立即出现 γδ T 细胞的显著增殖,并从刺激细胞中释放伽马干扰素(IFN-γ)、白细胞介素 17a(IL-17a)和 IL-12p40。增殖和细胞因子反应不仅在外周单核细胞中发现,而且在实验性攻毒后 10 周从肾淋巴结分离的淋巴细胞中也发现。总体而言,钩端螺旋体病疫苗接种和感染的影响很细微,仅导致 CD4 和 γδ T 细胞的适度激活。使用 Seppic Montanide 油乳剂佐剂可能会缩短对疫苗接种的反应启动,这在暴发期间或在钩端螺旋体病流行地区可能很有用。钩端螺旋体病是一种被低估、报告不足的人畜共患传染病,家畜可能是其携带者。作为 血清型 Hardjo 的储存宿主,牛可能会出现生殖问题,包括流产、出生弱仔或感染仔畜,或配种失败。尽管经过多年的研究和商业疫苗的应用,但对牛对疫苗接种和 攻毒的免疫反应的详细分析仍很缺乏。本研究使用一种选择用于增强细胞免疫反应的佐剂,评估了两种高效商业疫苗和一种新型菌苗的免疫反应。接种后可检测到针对特定抗原的 CD4 和 γδ T 细胞,并在刺激后与炎症细胞因子 IFN-γ 和 IL-17a 的释放有关。接种后第一周 CD4 和 γδ 细胞增加,与血清抗体一起,可能在从血液和常驻组织中清除细菌方面发挥作用。此外,在感染后可在局部淋巴结中发现这些抗原反应性 T 细胞,表明记忆反应可能不在循环中,但仍存在于局部淋巴结中。本研究中获得的信息扩展了对牛对钩端螺旋体病疫苗和感染的免疫反应的认识。油乳剂佐剂的使用可能会增强对钩端螺旋体菌苗的早期免疫反应,这在暴发期间或钩端螺旋体病流行地区可能很有用。