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Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response

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Abstract

The study explores the possibility of efficiently codelivering DNA vaccines and protein-based vaccines by formulation with aluminum phosphate (AlPO4). When mixed with aluminum adjuvants, plasmid DNA bound tightly onto aluminum hydroxide [Al(OH)3] but not to AlPO4. Different doses of DNA vaccines formulated with AlPO4 [but not Al(OH)3] induced enhanced humoral responses and supported priming of MHC class I restricted cellular immunity. Different proteins mixed with the plasmid DNA vaccine in the AlPO4 formulation did not impair its immunogenicity. Coinjection of two different vaccine-relevant antigens in the same AlPO4 formulation, one as a DNA vaccine and the other as a recombinant protein, elicited polyvalent, humoral, and cellular immune responses to all antigens delivered. The isotype profiles of the induced humoral responses and the cytokine profiles of the specifically primed T cell responses indicated that the combined vaccines supported copriming of Th1- and Th2-biased as well as balanced responses. These findings indicate that the AlPO4 adjuvant, a widely accepted adjuvant in human vaccination practice, can be used to combine protein- and DNA-based vaccination to prime an enhanced and balanced specific immunity.

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Abbreviations

CTL :

Cytotoxic T lymphocyte

HBcAg :

Hepatitis B core antigen

HBsAg :

Hepatitis B surface antigen

HEL :

Hen egg lysozyme

IFN :

Interferon

mAb :

Monoclonal antibody

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Acknowledgements

The excellent technical assistance of Ms T. Güntert and K. Ölberger are greatly appreciated. We thank Dr. K. Melber (RheinBiotech, Düsseldorf, Germany) for the recombinant HBsAg particles.

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Authors and Affiliations

  1. Institute for Medical Microbiology, University of Ulm, Albert Einstein Allee 11, 89081, Ulm, Germany

    Marcin Kwissa, Reinhold Schirmbeck & Joerg Reimann

  2. Brenntag Biosector, Frederikssund, Denmark

    Erik B. Lindblad

Authors
  1. Marcin Kwissa
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  2. Erik B. Lindblad
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  3. Reinhold Schirmbeck
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  4. Joerg Reimann
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Correspondence to Reinhold Schirmbeck.

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Kwissa, M., Lindblad, E.B., Schirmbeck, R. et al. Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response. J Mol Med 81, 502–510 (2003). https://doi.org/10.1007/s00109-003-0452-9

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  • DOI: https://doi.org/10.1007/s00109-003-0452-9

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