Co-administration of antigen with chemokine MCP-3 or MDC/CCL22 enhances DNA vaccine potency

Abstract

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.

Molecular cloning, expression and the adjuvant effects of interleukin-8 of channel catfish (Ictalurus Punctatus) against Streptococcus iniae

“…It has been reported that co-vaccination of antigens with cytokines is a novel and effective strategy to enhance immunization and regulate cellular and humoral immune responses to promote protective immunity against pathogens. Hence, cytokines used as the potential adjuvants have been studied increasingly 22 23 24 35 36 37 . IL-8 as a CXC chemokine produced by numerous cell types, was known to recruit neutrophils to inflammatory sites.…”

“…Cytokines are a family of low molecular weight and secretory proteins which involved in various pro-inflammatory functions against invasive pathogens including bacteria, virus or parasite. Chemokines as a kind of cytokines are among the adjuvants more widely used for vaccination against various pathogens in mammals 21 22 23 . To date, many cytokines and chemokines have been found in bony fish, and their functions and signaling are being explored with great progress 24 25 26 .…”

Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response

“…Chemokines and chemokine receptors contribute to leukocyte trafficking and recruitment to sites of inflammation. Indeed, XCL1, CCL3 (MIP1α), CCL5 (RANTES), CCL7, CCL20, CCL21, CCL22, CCL25, CCL27, CCL28, CXCL10 and CXCL13 have been demonstrated to significantly promote cellular and humoral responses when fused or co-delivered with antigens from viruses or tumors [11][12][13][14][15][16][17]. However, systematic evaluation of the immune response of chemokines after fusing with antigens has not been reported.…”