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

Author:

Williams-Macdonald Sarah E.1,Mitchell Mairi1,Frew David1,Palarea-Albaladejo Javier2ORCID,Ewing David2,Golde William T.1,Longbottom David1ORCID,Nisbet Alasdair J.1ORCID,Livingstone Morag1,Hamilton Clare M.1,Fitzgerald Stephen F.1,Buus Søren3,Bach Emil3ORCID,Dinkla Annemieke4,Roest Hendrik-Jan4,Koets Ad P.45ORCID,McNeilly Tom N.1ORCID

Affiliation:

1. Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK

2. Biomathematics and Statistics Scotland, JCMB, The King’s Buildings, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK

3. Department of Immunology & Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK 2200 Copenhagen, Denmark

4. Department of Bacteriology, Host-Pathogen Interaction and Diagnostics, Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands

5. Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, 3584 CL Utrecht, The Netherlands

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.

Funder

Department of Health and Social Care

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

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