title: A Novel Rabies Vaccine Expressing CXCL13 Enhances Humoral Immunity by Recruiting both T Follicular Helper and Germinal Center B Cells.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Yandi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.|Department of Pathology, University of Georgia, Athens, Georgia, USA.
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China zling604@yahoo.com.|College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000097:blood / Q000235:genetics*; D002633:Chemotaxis / Q000276:immunology; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology*; D056724:Immunity, Humoral; D051379:Mice; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011818:Rabies / Q000276:immunology / Q000517:prevention & control; D011819:Rabies Vaccines / Q000235:genetics* / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D054382:Chemokine CXCL13; D011819:Rabies Vaccines
keywords: CXCL13; T follicular helper cells; germinal center B cells; humoral immunity; rabies virus