Efficacy of Phase I and Phase II Coxiella burnetii Bacterin Vaccines in a Pregnant Ewe Challenge Model

Abstract

The bacterium Coxiella burnetii can cause the disease Q-fever in a wide range of animal hosts. Ruminants, including sheep, are thought to play a pivotal role in the transmission of C. burnetii to humans; however, the only existing livestock vaccine, namely, Coxevac® (Ceva Animal Health Ltd., Libourne, France), a killed bacterin vaccine based on phase I C. burnetii strain Nine-Mile, is only approved for use in goats and cattle. In this study, a pregnant ewe challenge model was used to determine the protective effects of Coxevac® and an experimental bacterin vaccine based on phase II C. burnetii against C. burnetii challenge. Prior to mating, ewes (n = 20 per group) were vaccinated subcutaneously with either Coxevac®, the phase II vaccine, or were unvaccinated. A subset of pregnant ewes (n = 6) from each group was then challenged 151 days later (~100 days of gestation) with 106 infectious mouse doses of C. burnetii, Nine-Mile strain RSA493. Both vaccines provided protection against C. burnetii challenge as measured by reductions in bacterial shedding in faeces, milk and vaginal mucus, and reduced abnormal pregnancies, compared to unvaccinated controls. This work highlights that the phase I vaccine Coxevac® can protect ewes against C. burnetii infection. Furthermore, the phase II vaccine provided comparable levels of protection and may offer a safer and cost-effective alternative to the currently licensed vaccine.

Efficacy and Safety of an Inactivated Phase I Coxiella burnetii Vaccine to Control Q Fever in Ruminants: A Systematic Review

“…In an experimental study already cited above [71], antibody (IgG) levels after two injections of Coxevac ® or the experimental phase II vaccine increased sharply above the ELISA kit's positivity threshold (S/P = 40%) but fell below this value 49 or 63 days after the second injection of Coxevac ® or the experimental vaccine, respectively. However, the S/P value remained at around 20% in vaccinated animals, which is higher than the value for non-vaccinated animals (0%).…”

“…In an experimental study [81], a slight transient hyperthermia was noted during the first injection or the booster injection, and a slight transient skin thickening appeared during the two primary vaccination injections; however, the authors concluded that the side effects of vaccination are minor although these differences were significant between vaccinated and control group after the first injection. In another experimental study [71], no local reactions were noted after the two primary injections, but there was a slight difference in rectal temperature (+0.68 °C) compared with the control group after the first injection (p < 0.001). After the second injection, no significant difference was noted between the groups regarding rectal temperature.…”

“…The studies related to vaccination in sheep are listed in Table 7. Like for goats, only one experimental study [71] assessed the efficacy of the vaccine to prevent contamination of ewes in a non-infected environment prior to vaccination and experimental challenge. It is important to note that the majority of studies were carried out before marketing authorisation was granted for sheep.…”

“…The clinical efficacy of Coxevac ® was demonstrated by an experimental challenge in pregnant ewes [71]. Animals were infected by a subcutaneous injection of 10 6 infective mouse doses (IMD) of C. burnetii 102 days after mating, corresponding to 130 days after the end of the vaccination protocol (two injections 21 days apart; n = 6).…”

“…In the study described above [71], C. burnetti shedding in faeces, vaginal fluids and milk was monitored from lambing or abortion until post-mortem examination, which took place around 4 weeks after abortion or lambing. With the exception of two ewes that temporarily shed the bacteria only in vaginal fluids (one and three days after lambing), none of the vaccinated ewes were shedders.…”