Oral Presentation The 2nd Prato Conference on the Pathogenesis of Bacterial Diseases of Animals 2012

Coxevac, Q fever vaccine:Vaccine production and control (#36)

Benaouda Kadra 1 , Miklos Tenk 1 , Balint Kupcsulik 1 , Christophe Manteca 2
  1. Ceva-Phylaxia Vet. Biol. Ltd., Budapest, Hungary
  2. Ceva Sante Animale, Libourne, France

Q fever is a zoonotic disease caused by C. burnettii, an obligatory intracellular bacterium that produces a highly resistant “spore-like” form1,2. Q fever affects humans and animals and it is endemic worldwide3 except New-Zealand4 but its prevalence is underestimated5. However, as diagnostic methods became more specific and easier to use, increasing number of cases are reported (e.g. acute human cases Bulgaria and The Netherlands). The shedding of C. burnettii by ruminants is considered as main source of the human infections6. The vaccination is an effective tool to control the disease.

The protective antigen of C. burnetii is the full-length phase I LPS7,8,9.  According to the statement of OIE “only vaccines containing or prepared from phase I C. burnetii should be considered protective”. Two marketed vaccines in the world are known that consist of exclusively phase I C. burnetii: Q-Vax (CSL, Australia) for human and Coxevac (Ceva, France) for veterinary applications.

The production of phase I antigen-based vaccine is performed in GMP biosafety-level 3 area. The process is rather complex, composed of bacteria cultivation on embryonated egg yolk sac, harvest, several downstream steps including inactivation and chemical extraction. The process is strictly controlled through specific ELISA methods to differentiate between phase I and II antigens, and to quantify antigen and egg-derived ballast protein contents for formulation.

The efficacy of the Q fever vaccine was demonstrated by vaccination and subsequent heterologous challenge in target species. The two main parameters to be assessed are the drastic decrease of abortion rate as well as the drop in the shedding of the bacterium10. A marketing authorisation (under exceptional circumstances) was obtained in September 2010 by Ceva in all EU member countries.

Coxevac vaccine combined with other complementary prophylactic measures has been successfully used in many EU countries to prevent Q fever in ruminants11,12,13,14

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  2. Guatteo R, Beaudeau F, Joly A, Seegers H. Coxiella burnetii shedding by dairy cows. Vet Res 2007 38:849-860.
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  4. Hilbink F, Penrose M, Kovacova E, Kazar J. Q fever is absent from New Zealand. Int J Epidemiol 1993 22:945-949.
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  6. Rodolakis A, Berri M, Héchard C, Caudron C, Souriau A, Bodier CC, Blanchard B, Camuset P, Devillechaise P, Natorp JC, Vadet JP, Arricau-Bouvery N. Comparison of Coxiella burnetii shedding in milk of dairy bovine, caprine, and ovine herds. J Dairy Sci 2007 90:5352-5360.
  7. Ormsbee RA, Bell EJ, Lackman DB, Tallent G. The influence of phase on the protective potency of Q fevervaccine. J Immunol 1964 92:404-412.
  8. Arricau-Bouvery N, Souriau A, Bodier C, Dufour P, Rousset E, Rodolakis A. Effect of vaccination with phase I and phase II Coxiella burnetii vaccines in pregnant goats. Vaccine 2005 23(35):4392-402.
  9. Zhang G, Russell-Lodrigue KE, Andoh M, Zhang Y, Hendrix LR, Samuel JE. Mechanisms of vaccine-induced protective immunity against Coxiella burnetii infection in BALB/c mice. J Immunol 2007 179:8372-8380.
  10. Souriau A, Arricau-Bouvery N, Bodier C, Rodolakis A. Comparison of the efficacy of Q fever vaccines against Coxiella burnetii experimental challenge in pregnant goats. Ann N Y Acad Sci 2003 990:521-523.
  11. Guatteo R, Seegers H, Joly A, Beaudeau F. Prevention of Coxiella burnetii shedding in infected dairy herds using a phase I C. burnetii inactivated vaccine. Vaccine 2008 26(34):4320-8. Epub 2008 Jun 30.
  12. Hogerwerf L, van den Brom R, Roest HI, Bouma A, Vellema P, Pieterse M, Dercksen D, Nielen M. Reduction of Coxiella burnetii prevalence by vaccination of goats and sheep, The Netherlands. Emerg Infect Dis 2011 17(3):379-86.
  13. Rousset E, Durand B, Champion JL, Prigent M, Dufour P, Forfait C, Marois M, Gasnier T, Duquesne V, Thiéry R, Aubert MF. Efficiency of a phase 1 vaccine for the reduction of vaginal Coxiella burnetii shedding in a clinically affected goat herd. Clin Microbiol Infect 2009 15 Suppl 2:188-9. Epub 2009 Sep 28.
  14. European Food Safety Authority. Scientific opinion on Q-fever. EFSA Journal 2010 8(5):1595