title: CCL17 combined with CCL19 as a nasal adjuvant enhances the immunogenicity of an anti-caries DNA vaccine in rodents.
abstract: OBJECTIVE
  CCL19 and its receptor CCR7 are essential molecules for facilitating the trafficking of mature dendritic cells (DCs) and helping to establish a microenvironment in lymphoid tissues to initiate primary immune responses, whereas CCL17 is required in the CCR7-CCL19-dependent migration of DCs. In this study we examined whether co-administration of CCL17 and CCL19 could enhance the immunogenicity of an anti-caries DNA vaccine, pCIA-P, in rodents.
  
  
  METHODS
  Plasmids encoding CCL17 (pCCL17/VAX) and CCL19 (pCCL19/VAX) were constructed. BALB/c mice were intranasally administered pCCL17/VAX, pCCL19/VAX, or pCCL17/VAX plus pCCL19/VAX, the migration of DCs to the spleen and draining lymph nodes (DLNs) was assessed with flow cytometry. The mice were co-administered pCIA-P; and the anti-PAc antibodies in the serum and saliva were detected with ELISA. Wistar rats were orally challenged with Streptococcus mutans and then administered pCIA-P in combination with pCCL17/VAX, pCCL19/VAX, or pCCL17/VAX plus pCCL19/VAX. The amount of S mutans sustained on rat molar surfaces was assessed using a colony forming assay. Caries activity was scored with the Keyes method.
  
  
  RESULTS
  Co-administration of the CCL17 and CCL19 genes in mice caused a greater increase in the number of mature DCs in the spleen and DLNs compared with administration of CCL17 or CCL19 genes alone. CCL17 and CCL19 double-adjuvant plus pCIA-P induced significantly higher levels of anti-PAc salivary IgA and anti-PAc serum IgG antibody in mice, and strengthened the ability of pCIA-P in inhibiting the colonization of S mutans on rat tooth surfaces. The caries activity of the combined adjuvant group was significantly lower than that of the pCCL17/VAX or the pCCL19/VAX group.
  
  
  CONCLUSIONS
  A nasal adjuvant consisting of a combination of CCL17 and CCL19 attracts more mature DCs to secondary lymphoid tissues, inducing enhanced antibody responses against the anti-caries DNA vaccine pCIA-P and reducing S mutans infection in rodents.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.|Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Pediatric Dentistry, School of Stomatology, Tongji University, Shanghai 200072, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Yan
authors.affiliation: Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zeng
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Cao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
authors.forename: Qing-An
authors.initials: QA
authors.lastname: Xu
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D054414:Chemokine CCL17 / Q000235:genetics / Q000276:immunology*; D054415:Chemokine CCL19 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D003731:Dental Caries / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000276:immunology; D008807:Mice, Inbred BALB C; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D054414:Chemokine CCL17; D054415:Chemokine CCL19; D016207:Cytokines; D019444:Vaccines, DNA