QuilA® adjuvanted Coxevac® sustains Th1-CD8+-type immunity and increases protection in Coxiella burnetii-challenged goats

Abstract

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.