KMID : 1039120160050020159
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Clinical and Experimental Vaccine Research 2016 Volume.5 No. 2 p.159 ~ p.168
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Safety and immunogenicity of recombinant rabies virus (ERAGS) in mice and raccoon dogs
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Yang Dong-Kun
Kim Ha-Hyun Choi Sung-Suk Kim Jong-Tack Lee Kang-Bok Lee Seong-Heon Cho In-Soo
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Abstract
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Purpose: The development of a genetically modified live rabies vaccine applicable to wild raccoon dogs is necessary for the eradication of rabies in Korea. Thus, we constructed a recombinant rabies virus (RABV) called the ERAGS strain, using a reverse genetic system and evaluated its safety and efficacy in mice and its safety and immunogenicity in raccoon dogs.
Materials and Methods: ERAGS, which has Asn194Ser and Arg333Glu substitutions in the glycoprotein, was constructed using site-directed mutagenesis. Mice were inoculated with the ERAGS strain (either 105.0 or 107.0 FAID50/mL) via intramuscular (IM) or intracranial injections and then challenged with a virulent RABV. Raccoon dogs were administered the ERAGS strain (108.0 FAID50/mL) either orally or via the IM route and the immunogenicity of the strain was evaluated using fluorescent antibody virus neutralization tests.
Results: The ERAGS strain inoculated into murine neuroblastoma cells reached 107.8 FAID50/mL at 96-hour post-inoculation. The virus was not pathogenic and induced complete protection from virulent RABV in immunized 4- and 6-week-old mice. Korean raccoon dogs immunized with the ERAGS strain via IM or oral route were also safe from the virus and developed high titer levels (26.4-32.8 IU/mL) of virus-neutralizing antibody (VNA) at 4 weeks post-inoculation.
Conclusion: The ERAGS RABV strain was effectively protective against rabies in mice and produced a high VNA titer in raccoon dogs.
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KEYWORD
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Rabies virus, Mouth, Vaccines, Raccoon dogs
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