Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration.
We have developed a method for the encapsulation of plasmid DNA in poly(DL-lactide-co-glycolide) microparticles. Encapsulated DNA, expressing the insect protein luciferase under the transcriptional control of the human cytomegalovirus immediate early promoter, was administered to mice by intraperitoneal injection or oral gavage. Intraperitoneal injection of encapsulated DNA elicited good serum IgG and IgM responses, and a modest IgA response. Oral administration stimulated good serum antibody responses in all three classes, and in addition, significant levels of mucosal IgA. PLG encapsulation thus has the ability to protect plasmid DNA against degradation after administration, and to facilitate its uptake into appropriate cells for the subsequent expression and presentation of antigen, in such a way as to elicit both systemic and mucosal antibody responses. These findings may have major implications for the design of novel vaccines and delivery strategies.
Jones
D H
DH
Centre for Applied Microbiology and Research, Porton Down, Salisbury, UK.
Corris
S
S
McDonald
S
S
Clegg
J C
JC
Farrar
G H
GH
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001672:Biocompatible Materials; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D004337:Drug Carriers; D017781:Genes, Immediate-Early / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D010957:Plasmids / Q000235:genetics; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011401:Promoter Regions, Genetic; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000914:Antibodies, Viral; D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D019444:Vaccines, DNA; D014765:Viral Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid