Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.

ANSES Technopôle agricole et vétérinaire Domaine de Pixérécourt Malzéville France

Institute of Food Safety Animal Health and Environment BIOR Riga Latvia

Istituto Zooprofilattico Sperimentale delle Venezie Viale dell'Università 10 Legnaro Italy

National Food and Veterinary Risk Assessment Institute of Lithuania J Kairiukscio Vilnius Lithuania; University of Applied Sciences Faculty of Agrotechnologies Vilnius district Lithuania

State Veterinary and Food Institute Zvolen Zvolen Slovak Republic

University of Veterinary and Pharmaceutical Sciences Brno Department of Infectious Diseases and Microbiology Brno Czech Republic

Veterinary Research Institute Hudcova 70 Brno Czech Republic

Zobrazit více v PubMed

ICTV. International Committee on Taxonomy of Viruses Family: Rhabdoviridae. Genus: Lyssavirus. ICTV official taxonomy; (2014). Available: http://ictvonline.org/virustaxonomy.asp

Hanlon CA, Childs JE. Epidemiology In: Jackson AC, editor. Rabies. Scientific basis of the disease and its management. 3rd ed. Oxford: Elsevier Academic Press; 2013. pp. 61–121.

Rosatte RC. Rabies control in wild carnivores In: Jackson AC editor. Rabies. Scientific basis of the disease and its management 3rd ed. Oxford: Elsevier Academic Press; 2013. pp. 617–670.

Cliquet F, Robardet E, Picard-Meyer E. Genetic strain modification of a live rabies virus vaccine widely used in Europe for wildlife oral vaccination. Antiviral Res. 2013; 100: 84–89. 10.1016/j.antiviral.2013.07.012 PubMed DOI

Cliquet F, Picard-Meyer E, Robardet E. Rabies in Europe: what are the risks? Expert Rev Anti Infect Ther. 2014; 12: 905–908. 10.1586/14787210.2014.921570 PubMed DOI

Morimoto K, Hooper DC, Carbaugh H, Fu ZF, Koprowski H, Dietzschold B. Rabies virus quasispecies: implications for pathogenesis. Proc Natl Acad Sci USA. 1998; 95: 3152–3156. PubMed PMC

Woo HJ, Reifman J. A quantitative quasispecies theory-based model of virus escape mutation under immune selection. Proc Natl Acad Sci USA. 2012; 109: 12980–12985. 10.1073/pnas.1117201109 PubMed DOI PMC

Capobianchi MR, Giombini E, Rozera G. Next-generation sequencing technology in clinical virology. Clin Microbiol Infect. 2013; 19: 15–22. 10.1111/1469-0691.12056 PubMed DOI

Borucki MK, Chen-Harris H, Lao V, Vanier G, Wadford DA, Messenger S, et al. Ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission. PLoS Negl Trop Dis. 2013; 7: e2555 10.1371/journal.pntd.0002555 PubMed DOI PMC

Geue L, Schares S, Schnick C, Kliemt J, Beckert A, Freuling C, et al. Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife. Vaccine. 2008; 26: 3227–3235. 10.1016/j.vaccine.2008.04.007 PubMed DOI

EDQM. Rabies vaccine (live, oral) for foxes and raccoon dogs Monograph 0746. European Pharmacopoeia 8.0 ed. Strasbourg: Council of Europe; 2014. pp. 1011–1012.

EDQM. Rabies vaccine (inactivated) for veterinary use Mongraph 0451. European Pharmacopoeia 7th ed ed. Strasbourg: Council of Europe; 2013. pp. 1008–1011.

WHO. WHO expert consultation on rabies- Second report Geneva: World Health Organization; 2013. PubMed

European commission. The oral vaccination of foxes against rabies Strasbourg: European commission—Health and Consumer Protection; 2002.

OIE. Principles of veterinary vaccine production Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Paris: OIE; 2015. pp. 1–15. available: http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/1.01.06_VACCINE_PRODUCTION.pdf

OIE. Rabies Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Paris: OIE; 2013. pp. 1–28. available: http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.13_RABIES.pdf

EFSA AHAW Panel. Update on oral vaccination of foxes and raccoon dogs against rabies. Scientific Panel on Animal Health and Welfare (AHAW). EFSA J. 2015; 13: 70 p.

Freuling CM, Hampson K, Selhorst T, Schroder R, Meslin FX, Mettenleiter TC, et al. The elimination of fox rabies from Europe: determinants of success and lessons for the future. Philos Trans R Soc Lond B Biol Sci. 2013; 368: 20120142 10.1098/rstb.2012.0142 PubMed DOI PMC

Cliquet F, Aubert M. Elimination of terrestrial rabies in Western European countries In: Schudel A, Lombard M., editors. Control of infectious animal diseases by vaccination. Basel: Karger; 2004. pp. 185–204. PubMed

Mahl P, Cliquet F, Guiot AL, Niin E, Fournials E, Saint-Jean N, et al. Twenty year experience of the oral rabies vaccine SAG2 in wildlife: a global review. Vet Res. 2014; 45: 77 10.1186/s13567-014-0077-8 PubMed DOI PMC

Kissi B, Badrane H, Audry L, Lavenu A, Tordo N, Brahimi M, et al. Dynamics of rabies virus quasispecies during serial passages in heterologous hosts. J Gen Virol. 1999; 80 (Pt 8): 2041–2050. PubMed