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

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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.

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Abbreviations

MCP-3:

monocyte chemotactic protein 3

MDC/CCL22:

macrophage-derived chemokine

BoNT/A:

botulinum neurotoxin serotype A

AHc-C:

C-terminal quarter of the heavy chain of botulinum neurotoxin serotype A

APCs:

antigen-presenting cells

DCs:

dendritic cells

IFA:

immunofluorescence assay

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Acknowledgments

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.

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Authors and Affiliations

  1. Pharmaceutical Institute, Henan University, Kaifeng, 475004, China

    Xinmei Xie, Lin Wang, Wenliang Yang, Ruishuang Yu, Qingli Li & Xiaobin Pang

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  1. Xinmei Xie
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  2. Lin Wang
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  3. Wenliang Yang
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  4. Ruishuang Yu
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  5. Qingli Li
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  6. Xiaobin Pang
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Correspondence to Xiaobin Pang.

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Xie, X., Wang, L., Yang, W. et al. Co-administration of antigen with chemokine MCP-3 or MDC/CCL22 enhances DNA vaccine potency. Invest New Drugs 33, 810–815 (2015). https://doi.org/10.1007/s10637-015-0250-6

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  • DOI: https://doi.org/10.1007/s10637-015-0250-6

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