Long-Term Immunogenicity and Efficacy of the Oral Rabies Virus Vaccine Strain SPBN GASGAS in Foxes

Abstract

: To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpes vulpes) were allocated to two treatment groups: group 1 (n = 31) received a vaccine bait containing 1.7 ml of the vaccine of minimum potency (106.6 FFU/mL) and group 2 (n = 15) received a placebo-bait. In total, 29 animals of group 1 and 14 animals of group 2 were challenged at 12 months post-vaccination with a fox rabies virus isolate (103.0 MICLD50/mL). While 90% of the animals offered a vaccine bait resisted the challenge, only one animal (7%) of the controls survived. All animals that had seroconverted following vaccination survived the challenge infection at 12 months post-vaccination. Rabies specific antibodies could be detected as early as 14 days post-vaccination. Based on the kinetics of the antibody response to SPBN GASGAS as measured in ELISA and RFFIT, the animals maintained stable antibody titres during the 12-month pre-challenge observation period at a high level. The results indicate that successful vaccination using the oral route with this new rabies virus vaccine strain confers long-term duration of immunity beyond one year, meeting the same requirements as for licensure as laid down by the European Pharmacopoeia.

Comparable Long-Term Rabies Immunity in Foxes after IntraMuscular and Oral Application Using a Third-Generation Oral Rabies Virus Vaccine

“…A total of twenty-two female captive-reared, seronegative foxes aged 2–3 months were randomly allocated to three treatment groups. Animals in group 1 ( n = 11) were part of a long-term efficacy study and received a vaccine bait containing the vaccine strain SPBN GASGAS (Genbank accession number MH660455 titer of 10 6.6 FFU/mL) [ 20 ], while animals in group 2 ( n = 6) were inoculated parenterally with 0.5 mL of the vaccine with the same titer in the gluteus muscles of the right hind leg. Group 3 ( n = 5) received a placebo-bait.…”

“…At 365 dpv, all animals were challenged intramuscularly ( Musculus masseter ) with 10 3.0 MICLD50/dose of rabies field virus strain “fox Krefeld” (FLI ID 148¸ Genbank accession number LN879481.2) [ 19 , 20 ] and monitored for 90 days post infection (dpi). Humane clinical endpoints were defined as described elsewhere [ 44 ].…”

“…Humane clinical endpoints were defined as described elsewhere [ 44 ]. All surviving animals were euthanized 90 dpi (equals 455 dpv) as described [ 19 , 20 ]. The study was conducted in accordance with national and European regulations, and European guidelines on animal welfare from the Federation of European Laboratory Animal Science Associations (FELASA) [ 20 ].…”

“…All surviving animals were euthanized 90 dpi (equals 455 dpv) as described [ 19 , 20 ]. The study was conducted in accordance with national and European regulations, and European guidelines on animal welfare from the Federation of European Laboratory Animal Science Associations (FELASA) [ 20 ]. The animal study was approved by the Ethics Committee of the Federal State of Mecklenburg-Western Pomerania, Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei Mecklenburg-Vorpommern, 18003 Rostock, Germany (FLI-7221.3-1-087/16).…”

“…Live-attenuated RABVs are known to replicate rapidly, express large amounts of glycoprotein (G), and induce strong immune responses that can clear a RABV infection [ 6 , 7 , 8 , 9 ]. Their efficacy has been demonstrated in a variety of wild carnivore reservoir species [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Conventionally, the effectiveness of rabies vaccines in wildlife target species is determined by serological testing [ 24 ], e.g., the detection of rabies virus neutralizing (VNA) or binding antibodies as a surrogate for humoral immune response and hence, adequate B-cell response [ 25 ].…”