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Liposome/DNA complexes coated with biodegradable PLA improve immune responses to plasmid encoding hepatitis B surface antigen
Author(s) -
Bramwell Vincent W.,
Eyles Jim E.,
Somavarapu Satyanarayana,
Alpar H. Oya
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01448.x
Subject(s) - naked dna , dna vaccination , antigen , immune system , antibody , microbiology and biotechnology , splenocyte , biology , genetic enhancement , plasmid , in vivo , gene gun , liposome , immunization , virology , dna , immunology , biochemistry , gene
Summary We hypothesized that the addition of polymer to the surface of liposome/DNA complexes may potentially enhance in vivo delivery of plasmid DNA to antigen‐presenting cells and thereby facilitate enhanced immune responses to encoded protein. BALB/c mice were immunized subcutaneously or intramuscularly three times with a total of 50 µg of the plasmid pRc/CMV‐HBs(S) (ayw subtype) encoding for the hepatitis B surface antigen. We measured transgene‐specific total immunoglobulin G (IgG), IgG2a, IgG2b and IgG1 antibody responses as well as splenocyte and T‐cell proliferation and cytokine production upon re‐stimulation following immunization. Modification of lipid/DNA complexes by the polymer precipitation method used here for the addition of poly( d , l ‐lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene‐specific immune responses to plasmid‐encoded antigen when administered by the subcutaneous route. In addition, the polymer‐modified formulations delivered by this route were more effective than naked DNA delivered by the intramuscular route in inducing antibody responses ( n =5, P <0·03). Our observations provide ‘proof of principle’ for the use of these multicomponent formulations, which offer potential for manipulation and increased transfection efficiency in vivo for the purposes of genetic immunization.