Tomaiuolo Sara, Jansen Wiebke, Soares Martins Susana, Devriendt Bert, Cox Eric, Mori Marcella
Bacterial Zoonoses Unit, Veterinary Bacteriology, Infectious Diseases in Animals Scientific Directorate, Sciensano, Brussels, Belgium.
National Reference Centre for Coxiella burnetii and Bartonella, Brussels, Belgium.
NPJ Vaccines. 2023 Feb 14;8(1):17. doi: 10.1038/s41541-023-00607-z.
Coxevac® is the EMA-approved veterinary vaccine for the protection of cattle and goats against Q fever, a zoonotic bacterial disease due to Coxiella burnetii. Since Coxevac® reduces bacterial shedding and clinical symptoms but does not prevent infection, novel, ready-to-use vaccine formulations are needed to increase its immunogenicity. Here, a goat vaccination-challenge model was used to evaluate the impact of the commercially available saponin-based QuilA® adjuvant on Coxevac® immunity. Upon challenge, the QuilA®-Coxevac® group showed a stronger immune response reflected in a higher magnitude of total IgG and an increase in circulating and splenic CD8 T-cells compared to the Coxevac® and challenged-control groups. The QuilA®-Coxevac® group was characterized by a targeted Th1-type response (IFNγ, IP10) associated with increased transcripts of CD8 and NK cells in spleens and γδ T cells in bronchial lymph nodes. Coxevac® vaccinated animals presented an intermediate expression of Th1-related genes, while the challenged-control group showed an immune response characterized by pro-inflammatory (IL1β, TNFα, IL12), Th2 (IL4 and IL13), Th17 (IL17A) and other immunoregulatory cytokines (IL6, IL10). An intriguing role was observed for γδ T cells, which were of TBX21- and SOX4-types in the QuilA®-Coxevac® and challenged control group, respectively. Overall, the addition of QuilA® resulted in a sustained Th1-type activation associated with an increased vaccine-induced bacterial clearance of 33.3% as compared to Coxevac® only. QuilA® could be proposed as a readily-applied veterinary solution to improve Coxevac® efficacy against C. burnetii infection in field settings.
Coxevac®是一种经欧洲药品管理局(EMA)批准的兽用疫苗,用于保护牛和山羊免受Q热侵害,Q热是一种由伯氏考克斯体引起的人畜共患细菌性疾病。由于Coxevac®可减少细菌排出和临床症状,但不能预防感染,因此需要新型即用型疫苗制剂来提高其免疫原性。在此,使用山羊疫苗接种-攻毒模型来评估市售的基于皂苷的QuilA®佐剂对Coxevac®免疫的影响。攻毒后,与Coxevac®组和攻毒对照组相比,QuilA®-Coxevac®组表现出更强的免疫反应,表现为总IgG水平更高,循环和脾脏CD8 T细胞增加。QuilA®-Coxevac®组的特征是靶向Th1型反应(IFNγ、IP10),与脾脏中CD8和NK细胞以及支气管淋巴结中γδ T细胞的转录本增加有关。接种Coxevac®的动物呈现Th1相关基因的中等表达,而攻毒对照组的免疫反应特征是促炎(IL1β、TNFα、IL12)、Th2(IL4和IL13)、Th17(IL17A)和其他免疫调节细胞因子(IL6、IL10)。观察到γδ T细胞具有有趣的作用,在QuilA®-Coxevac®组和攻毒对照组中分别为TBX21型和SOX4型。总体而言,添加QuilA®导致持续的Th1型激活,与仅使用Coxevac®相比,疫苗诱导的细菌清除率提高了33.3%。QuilA®可被提议作为一种易于应用的兽用解决方案,以提高Coxevac®在野外环境中对抗伯氏考克斯体感染的功效。