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Enhancement of plasmid DNA immunogenicity with linear polyethylenimine
Author(s) -
Grant Evita V.,
Thomas Mini,
Fortune Jennifer,
Klibanov Alexander M.,
Letvin Norman L.
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201242410
Subject(s) - immunogenicity , polyethylenimine , biology , immunogen , dna vaccination , microbiology and biotechnology , dna , recombinant dna , plasmid , antigen , immunology , biochemistry , transfection , antibody , gene , monoclonal antibody
The utility of plasmid DNA as an immunogen has been limited by its weak immunogenicity. In the present study, we evaluated the ability of a family of linear polyethylenimine ( PEI ) polymers, complexed to plasmid DNA , to augment DNA expression in vivo and to enhance antigen‐specific adaptive immune responses. We showed that four of five structurally different PEI s that we evaluated increased in vivo DNA expression 20‐ to 400‐fold, and enhanced DNA ‐induced epitope‐specific CD 8+ T ‐cell responses 10‐ to 25‐fold in BALB /c and C 57 BL /6 J mice respectively, when delivered intravenously. Functional studies of the PEI ‐ DNA ‐induced CD 8+ T ‐cell responses demonstrated that formulation of DNA with PEI was associated with increased numbers of cells secreting type I cytokines. In addition, PEI ‐ DNA complexes improved antigen‐specific T H 1‐helper cell and humoral responses. Most importantly, the PEI ‐ DNA complexes elicited memory cellular responses, capable of rapid expansion and accelerated clearance of a lethal dose of recombinant Listeria monocytogenes . Lastly, we identified physical properties of PEI ‐ DNA complexes that are associated with enhanced DNA ‐elicited immunogenicity. These findings demonstrate that PEI polymers can play an important role in the development of DNA ‐based vaccines in the setting of infectious disease prevention and cancer therapy.