title: Expression of interleukin-6 by a recombinant rabies virus enhances its immunogenicity as a potential vaccine.
abstract: Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain. Moreover, survival rates of mice immunized with rHEP-CaIL6 were higher compared with mice immunized with parent HEP-Flury according to the challenge assay. Flow cytometry further confirmed that immunization with rHEP-CaIL6 induced the strong recruitment of mature B cells and CD8+T cells to lymph nodes, which may partially explain the high levels of VNA and enhanced cellular immunity. Quantitative real-time PCR indicated that rHEP-CaIL6 induced stronger inflammatory and immune responses in the central nervous system, which might have allowed virus clearance in the early infection phase. Furthermore, mice infected intranasally with rHEP-CaIL6 developed no clinical symptoms while mice infected with HEP-Flury showed piloerection. In summary, these data indicate that rHEP-CaIL6 induces a strong, protective immune response with a good safety profile. Therefore, a recombinant RABV strain expressing canine IL6 may aid the development of an effective, safe attenuated rabies vaccine.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Boyue
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tian
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Lyu
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Mei
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China. Electronic address: ywluo@scau.edu.cn.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Luo
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China. Electronic address: xfguo@scau.edu.cn.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002465:Cell Movement / Q000187:drug effects; D004285:Dogs; D005260:Female; D015870:Gene Expression; D007114:Immunization; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011818:Rabies / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011819:Rabies Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D011820:Rabies virus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015850:Interleukin-6; D011819:Rabies Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
keywords: Adjuvant; HEP-Flury; IL6; Rabies virus; Vaccine