Te Kamp Verena, Friedrichs Virginia, Freuling Conrad M, Vos Ad, Potratz Madlin, Klein Antonia, Zaeck Luca M, Eggerbauer Elisa, Schuster Peter, Kaiser Christian, Ortmann Steffen, Kretzschmar Antje, Bobe Katharina, Knittler Michael R, Dorhoi Anca, Finke Stefan, Müller Thomas
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut (FLI), WHO Collaborating Centre for Rabies Surveillance and Research, OIE Reference Laboratory for Rabies, 17493 Greifswald-Insel Riems, Germany.
Boehringer Ingelheim GmbH, 55216 Ingelheim am Rhein, Germany.
Vaccines (Basel). 2021 Jan 14;9(1):49. doi: 10.3390/vaccines9010049.
The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.
活的基因工程口服狂犬病病毒（RABV）变体SPBN GASGAS在狐狸中可诱导持久免疫力，并且在通过实验性口服和肠胃外给药途径接种后，能保护狐狸免受致死剂量的狂犬病病毒野毒株攻击。口服和肠胃外接种疫苗的狐狸中，狂犬病病毒特异性结合抗体和免疫球蛋白同种型（IgM、总IgG、IgG1、IgG2）的诱导情况相当。仅在病毒中和（VNA）滴度的诱导方面观察到差异，肠胃外接种疫苗组的VNA滴度显著更高。攻毒前后（接种疫苗后365天）狂犬病特异性抗体的动态变化表明，SPBN GASGAS的1型免疫保护占主导地位。无论给药途径如何，在缺乏IgG1的情况下，对SPBN GAGAS的免疫反应主要由IgG2驱动。有趣的是，用SPBN GASGAS接种疫苗不会使接种动物的诱导性IFN-γ产生有显著差异，这表明在攻毒期间细胞免疫反应相对较弱。值得注意的是，SPBN GASGAS的肠胃外应用未在狐狸中引起任何不良副作用，因此支持了这种口服狂犬病疫苗在各种物种中的安全性研究。
