The immune response to a Coxiella burnetii vaccine in sheep varies according to their natural pre-exposure.

Q fever in humans is caused by Coxiella (C.) burnetii. In 2008 and 2012, cases of Q fever in humans were linked to an infected flock of approximately 650 ewes. Since 2013 gimmers (G'13, G'14, G'15 etc.) were primary vaccinated (two doses) with an inactivated C.burnetii vaccine without any revaccination. In 2013, 30 ewes were primary vaccinated (A'13). Shedding was annually monitored by qPCR-testing of vaginal and nasal swabs collected at lambing. Animals were tested for Phase I- (PhI) and PhII-antibodies (Ab) and for PhII-specific-interferon-γ (IFN-γ) before and after vaccination. The effect of a revaccination was determined in 2018 and 2023. Groups of randomly selected gimmers primary vaccinated in 2015, 2016 and 2017 and a mixed group of older animals (A'13, G'13 and G'14) were revaccinated once in 2018. The trial was repeated in 2023 on groups primary vaccinated in 2019-2023. Major shedding after the outbreak in 2012 ceased in 2014. Thereafter C.burnetii was only sporadically detected at low-level in 2018, 2021 and 2023. Sheep naturally exposed to C.burnetii during the outbreak in 2012 (A'13, G'13) mounted a strong and complete (PhI, PhII, IFN-γ) recall immune response after vaccination. A serological PhI+/PhII+ pattern dominated after vaccination. In contrast, since 2014 a weaker immune response (PhII-titre, IFN-γ) and a dominance of the PhI-/PhII+ pattern was observed in vaccinated gimmers. The number of serologically non-responding gimmers to vaccination increased to 25.0 % in G'16/G'17 and 40.4 % in G'19/G'20. But revaccination even three (G'15 in 2018) and four (G'19 in 2023) years after primary vaccination resulted in a strong and complete immune response. No difference of the immune response nor to more recently primary vaccinated animals (G'23 in 2023) nor to those animals that were present during the outbreak (A'13/G'13/G'14 in 2018) was observed.