Recombinant rabies virus expressing IL-15 enhances immunogenicity through promoting the activation of dendritic cells in mice
Rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. Interleukin (IL)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. In this study, IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus (RABV) strain LBNSE (designated as LBNSE-IL15), and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated. It was found that mice vaccinated with LBNSE-IL15 could induce significantly higher level of virus-neutralizing antibody (VNA) than those immunized with LBNSE, resulting in the higher protection after challenge. Further investigation was performed to find out the possible role of IL-15 plays in the process of antibody induction, and it was found that LBNSE-IL15 could enhance the maturation of dendritic cells (DCs) in immunized mice. Furthermore, the mice immunized with LBNSE-IL15 could promote the TFH cells differentiation and the generation of germinal center B cells and plasma cells. Together, these data indicated that IL-15 could be a potential adjuvant in enhancing the immunogenicity of RABV, contributing to the development of more-efficacious rabies vaccines.
Keywordsrabies interleukin-15 dendritic cells germinal center plasma cells
Unable to display preview. Download preview PDF.
This study was partially supported by the National Natural Science Foundation of China (31402176, 31372419, 31522057), the National Program on Key Research Project of China (2016YFD0500400), the Fundamental Research Funds for the Central Universities (2662016 QD036, to MZ); the Ministry of Science and Technology of China (863 program, number 2011AA10A212), and the Ministry of Agriculture of China (special fund for Agro-scientific research in the Public Interest, 2013 03042, to ZFF).
- Chen J, Li ZY, Huang SY, Petersen E, Song HQ, Zhou DH, Zhu XQ. 2014. Protective efficacy of Toxoplasma gondii calciumdependent protein kinase 1 (TgCDPK1) adjuvated with recombinant IL-15 and IL-21 against experimental toxoplasmosis in mice. BMC Infect Dis, 14: 487.CrossRefPubMedPubMedCentralGoogle Scholar
- Pagliari D, Frosali S, Landolfi R, Cianci R. 2013. The Role of IL-15 in Human Cancer: Friend or Foe?. Int Trends Immun, 1: 35–42.Google Scholar
- Kutzler MA, Robinson TM, Chattergoon MA, Choo DK, Choo AY, Choe PY, Ramanathan MP, Parkinson R, Kudchodkar S, Tamura Y, et al. 2005. Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol, 175: 112–123.CrossRefPubMedGoogle Scholar
- Wang Z, Li M, Zhou M, Zhang Y, Yang J, Cao Y, Wang K, Cui M, Chen H, Fu ZF, Zhao L. 2017. A Novel Rabies Vaccine Expressing CXCL13 Enhances Humoral Immunity by Recruiting both T Follicular Helper and Germinal Center B Cells. J Virol, 91. doi: 10.1128/JVI.01956-16Google Scholar