Co-delivery of ccl19 gene enhances anti-caries DNA vaccine pCIA-P immunogenicity in mice by increasing dendritic cell migration to secondary lymphoid tissues

Abstract

Aim: To investigate how co-delivery of the gene encoding C-C chemokine affected the systemic immune responses to an anti-caries DNA vaccine pCIA-P in mice. Methods: Plasmid encoding CCL19-GFP fusion protein (pCCL19/GFP) was constructed by inserting murine ccl19 gene into GFPexpressing vector pAcGFP1-N1. Chemotactic effect of the fusion protein on murine dendritic cells (DCs) was assessed in vitro and in vivo using transwell and flow cytometric analysis, respectively. BALB/c mice were administered anti-caries DNA vaccine pCIA-P plus pCCL19/GFP (each 100 μg, im) or pCIA-P alone. Serum level of anti-PAc IgG was assessed with ELISA. Splenocytes from the mice were stimulated with PAc protein for 48 h, and IFN-γ and IL-4 production was measured with ELISA. The presence of pCCL19/GFP in spleen and draining lymph nodes was assessed using PCR. The expression of pCCL19/GFP protein in these tissues was analyzed under microscope and with flow cytometry. Results: The expression level of CCL19-GFP fusion protein was considerably increased 48 h after transfection of COS-7 cells with pCCL19/GFP plasmids. The fusion protein showed potent chemotactic activity on DCs in vitro. The level of serum PAc-specific IgG was significantly increased from 4 to 14 weeks in the mice vaccinated with pCIA-P plus pCCL19/GFP. Compared to mice vaccinated with pCIA-P alone, the splenocytes from mice vaccinated with pCIA-P plus pCCL19/GFP produced significantly higher level of IFN-γ, but IL-4 production had no significant change. Following intromuscular co-delivery, pCCL19/GFP plasmid and fusion protein were detected in the spleen and draining lymph nodes. Administration of CCL19 gene in mice markedly increased the number of mature DCs in secondary lymphoid tissues. Conclusion: CCL19 serves as an effective adjuvant for anti-caries DNA vaccine by inducing chemotactic migration of DCs to secondary lymphoid tissues.

CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue

“…Although multiple factors influence immunization outcomes, our findings provide one explanation for the failure of CCL19, as an adjuvant, to boost immune response to HIV-1 VLPs in a previous study (54), in which a lower dose (50 mg/mouse) of pCCL19 was used. We (75) and other investigators (40) clearly observed that pCCL19, when delivered at 100 mg/ mouse, had modulating effects in enhancing Ag-specific responses to HIV-1 gp140, HSV-1 gB, and the PAc Ag of Streptococcus mutans. DNA immunization is most commonly used in conjunction with alternative boosting strategies, such as the use of viral vectors or recombinant proteins.…”

RETRACTED ARTICLE: Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region ofS. mutansglucosyltransferase effectively prevents caries formation in rodents

“…Moreover, DC-based anticaries vaccines are well developed. 22 The size of the nanoparticle might influence the efficiency of their uptake by DCs. For example, smaller nanoparticles (»20 nm in diameter) are more immunogenic compared with larger nanoparticles (»500 nm in diameter), even after a single immunization.…”

CCL17 combined with CCL19 as a nasal adjuvant enhances the immunogenicity of an anti-caries DNA vaccine in rodents

“…CCL19, which is secreted by stromal cells in the T-cell area of DLNs, is a high-affinity functional ligand for CCR7. Our previous findings showed that CCL19 is a potent chemoattractant for in vitro-expanded bone marrow-derived DCs, and the specificity was confirmed by CCR7 blockade of mature DCs [20] . In this study, we showed that exogenous overexpression of CCL19 enhanced the recruitment of DCs to DLNs.…”

“…Our previous studies showed that a CCL19 DNA plasmid entered the secondary lymphoid tissues and expressed the chemokine there following intramuscular administration. Using a CCL19 plasmid in combination with the anti-caries DNA vaccine pCIA-P, an increased serum PAc-specific IgG level was observed [20] . To date, by virtue of its paramount importance in diverse effects on DC and lymphocyte migration and immune response formation, it has been postulated that CCL19 is an interesting candidate vaccine adjuvant for a number of infectious diseases [19,32,33] .…”

“…Our previous study demonstrated that the codelivery of the CCL19 gene with the anti-caries DNA vaccine pCIA-P significantly augmented systemic immune responses. Moreover, an increased number of mature DCs were detected in the DLNs of mice following the co-administration of CCL19 DNA [20] . These results indicate that the elevated immune responses in CCL19-coadministered mice occurred as a result of increased DC-T cell encounters in the secondary lymphoid tissues.…”