Expression of interleukin-6 by a recombinant rabies virus enhances its immunogenicity as a potential vaccine |
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| Institution: | 1. Universidad de Almería, Spain;2. Universitat Oberta de Catalunya, Center for Demographic Sudies (Universitat Autònoma de Barcelona), Spain;1. Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, Hungária krt. 23–25, 1143 Budapest, Hungary;2. Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Hungária krt. 21, 1143 Budapest, Hungary;3. Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria;1. Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India;2. Centre for Animal Disease Research and Diagnosis, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India;3. Animal Science Section, ICAR-Central Coastal Agricultural Research Institute, Ela, Goa, India;4. Cancer Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Canada;5. ICAR-National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, Karnataka, India |
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| 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. |
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| Keywords: | Rabies virus HEP-Flury IL6 Vaccine Adjuvant |
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