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PLoS One. 2015 Apr 13;10(4):e0123113. doi: 10.1371/journal.pone.0123113. eCollection 2015.

Immunomodulator-based enhancement of anti smallpox immune responses.

Author information

1
Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
2
Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico; Department of Microbiology Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico.
3
Department Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
4
Department of Biology, University of Puerto Rico, Humacao, Puerto Rico; Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico; Center for Applied Tropical Ecology and Conservation, University of Puerto Rico, Rio Piedras campus, San Juan, Puerto Rico.
5
Department of Microbiology Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico.

Abstract

BACKGROUND:

The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.

METHODS:

We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.

RESULTS:

The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.

CONCLUSION:

These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

PMID:
25875833
PMCID:
PMC4395221
DOI:
10.1371/journal.pone.0123113
[Indexed for MEDLINE]
Free PMC Article

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