Abstract:
Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.
摘要:
马红球菌(R.equi)是一种人畜共患的机会性病原体,主要导致马驹和免疫功能低下的个体致命的肺和肺外脓肿。迄今为止,不存在针对马氏R.的商业疫苗。我们先前使用反向疫苗学方法从R.equi的完整基因组中筛选了所有潜在的疫苗候选物。其中五位候选人,即ABC转运蛋白底物结合蛋白(ABC转运蛋白),青霉素结合蛋白2(PBD2),NlpC/P60家族蛋白(NlpC/P60),酯酶家族蛋白(酯酶),选择和M23家族金属肽酶(M23)用于评估在R.equi攻击的BALB/c小鼠模型中的免疫原性和免疫保护作用。结果表明,所有5只候选疫苗免疫小鼠的脾抗原特异性IFN-γ和TNF-α阳性CD4+和CD8+T淋巴细胞均显著增加,并产生强烈的Th1型和Th2型免疫反应和抗体反应。R.equi挑战两周后,与对照组相比,用五种候选疫苗免疫可减少肺部细菌负荷,并改善肺部和肝脏的病理损伤。NlpC/P60,酯酶,M23比ABC转运体和PBD2更有效地诱导小鼠抵抗R.equi攻击的保护性免疫。此外,这些候选疫苗具有诱导小鼠T淋巴细胞记忆免疫应答的潜力。总之,这些抗原是开发针对马氏杆菌的保护性疫苗的有效候选物。马氏R.equi抗原库得到了扩展,为多价疫苗的开发提供了新思路。