Co-administration of antigen with chemokine MCP-3 or MDC/CCL22 enhances DNA vaccine potency
- 170 Downloads
We evaluated the utility of chemokine MCP-3 and MDC/CCL22 as molecular adjuvants of DNA vaccines for botulinum neurotoxin serotype A (BoNT/A) in a Balb/c mouse model. Notably, the immunogenicity of the DNA vaccine against BoNT/A was not enhanced using a fusion of the AHc-C antigen with the MCP-3 or MDC/CCL22. Nevertheless, the potency of the DNA vaccine was significantly modulated and enhanced by co-administration of the AHc-C antigen with MCP-3 or MDC/CCL22. This strategy elicited high levels of humoral immune responses and protection against BoNT/A. The enhanced potency was further boosted by co-administration of the AHc-C antigen with both MCP-3 and MDC/CCL22 in Balb/c mice, but not by co-administration of AHc-C antigen with the MCP-3-MDC/CCL22 fusion. Co-immunization with both the MCP-3 and MDC/CCL22 constructs induced the highest levels of humoral immunity and protective potency against BoNT/A. Our results indicated that MCP-3 and MDC/CCL22 are effective molecular adjuvants of the immune responses induced by the AHc-C-expressing DNA vaccine when delivered by co-administration of the individual chemokines, but not when delivered in the form of a chemokine/antigen fusion. Thus, we describe an alternative strategy to the design and optimization of DNA vaccine constructs based on co-administration of the antigen with the chemokine rather than in the form of a chemokine/antigen fusion.
KeywordsDNA vaccine MCP-3 MDC/CCL22 Co-administration Molecular adjuvant
monocyte chemotactic protein 3
botulinum neurotoxin serotype A
C-terminal quarter of the heavy chain of botulinum neurotoxin serotype A
The authors gratefully acknowledge the support provided by the Chinese National Natural Science Fund No. 81273652.
Conflict of Interest
The authors declare no conflict of interest.
- 18.Sumida SM, McKay PF, Truitt DM, Kishko MG, Arthur JC, Seaman MS, Jackson SS, Gorgone DA, Lifton MA, Letvin NL, Barouch DH (2004) Recruitment and expansion of dendritic cells in vivo potentiate the immunogenicity of plasmid DNA vaccines. J Clin Invest 114(9):1334–1342PubMedCentralPubMedCrossRefGoogle Scholar
- 30.Zhang X, Divangahi M, Ngai P, Santosuosso M, Millar J, Zganiacz A, Wang J, Bramson J, Xing Z (2007) Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: Enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene. Vaccine 25(7):1342–1352PubMedCrossRefGoogle Scholar