A Novel Rabies Vaccine Expressing CXCL13 Enhances Humoral Immunity by Recruiting both T Follicular Helper and Germinal Center B Cells
| Autor: | Yajing Zhang, Kunlun Wang, Huanchun Chen, Jie Yang, Yandi Cao, Mingming Li, Min Cui, Zhen F. Fu, Ming Zhou, Zhao Wang, Ling Zhao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Rabies Plasma Cells Immunology Gene Expression Biology medicine.disease_cause Microbiology Mice 03 medical and health sciences 0302 clinical medicine Rabies vaccine Immune system Cricetinae Virology Vaccines and Antiviral Agents medicine Animals CXCL13 B cell B-Lymphocytes Chemotaxis Immunogenicity Rabies virus Germinal center Dendritic Cells T-Lymphocytes Helper-Inducer Germinal Center medicine.disease Chemokine CXCL13 Immunity Humoral 030104 developmental biology medicine.anatomical_structure Rabies Vaccines 030220 oncology & carcinogenesis Insect Science medicine.drug |
| Zdroj: | Journal of Virology. 91 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01956-16 |
| Popis: | Rabies remains a public health threat in most parts of the world, and approximately 99% of the cases are transmitted by dogs. There is an urgent need to develop an efficacious and affordable vaccine to control canine-transmitted rabies in developing countries. Our previous studies demonstrate that overexpression of chemokines/cytokines such as CCL-3 (MIP-1α) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance the immunogenicity of rabies vaccines. In the present study, the chemokine CXCL13 was inserted into the genome of the recombinant rabies virus (rRABV) strain LBNSE, and the effect of the chemokine CXCL13 on the immunogenicity of RABV was investigated. It was found that LBNSE-CXCL13 recruited follicular helper T (Tfh) and germinal center (GC) B cells, promoted the formation of GCs, and increased the population of plasma cells in immunized mice. Further studies showed that mice immunized with LBNSE-CXCL13 produced more rabies virus-neutralizing antibodies (VNAs) and developed better protection than those immunized with the parent virus LBNSE or the GM-CSF-expressing RABV (LBNSE-GM-CSF). Collectively, these findings provide a better understanding of the role of CXCL13 expression in the immunogenicity of the RABV, which may help in designing more-efficacious rabies vaccines. IMPORTANCE Rabies is endemic in most parts of the world, and more effort is needed to develop affordable and effective vaccines to control or eliminate this disease. The chemokine CXCL13 recruits both Tfh and B cells, which is essential for the homing of Tfh cells and the development of B cell follicles. In this study, the effect of the overexpression of CXCL13 on the immunogenicity of the RABV was evaluated in a mouse model. We found that CXCL13 expression promoted humoral immunity by recruiting Tfh and GC B cells, facilitating the formation of GCs, and increasing the number of plasma cells. As expected, the overexpression of CXCL13 resulted in enhanced virus-neutralizing antibody (VNA) production and protection against a virulent RABV challenge. These findings provide a better understanding of the role of CXCL13 in RABV-induced immune responses, which will help in designing more efficacious rabies vaccines. |
| Databáze: | OpenAIRE |
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