title: PLGA-dendron nanoparticles enhance immunogenicity but not lethal antibody production of a DNA vaccine against anthrax in mice.
abstract: Dendriplexes, complexes of dendrons and condensed plasmids containing the gene for protective antigen (PA) of Bacillus anthracis, were encapsulated in poly-lactide-co-glycolide (PLGA) particles using the double emulsion method. The two dendrons employed are a dendron with three C(18) chains (C(18) dendron) and one with no attached hydrocarbon chains (the C(0) dendron). Three types of particles were examined, namely PLGA-C(18) dendriplexes, PLGA-C(0) dendriplexes and the control PLGA-naked DNA system. These were characterised by standard biophysical methods such as photon correlation spectroscopy (PCS) and scanning electron microscopy to select the complexes for in vivo testing. Three intramuscular immunizations were carried out using 14 microg of DNA per dose at weekly intervals in BALB/c mice. Antibodies against rPA were measured using ELISA. Results indicate that the PLGA-C(18) dendriplex particles produced superior levels of anti-PA IgG antibodies in comparison to animals immunized with the PLGA-C(0) dendriplex particles. The level of antibody production was dependent on the number of immunizations, higher antibody levels being measured after two booster vaccinations. However toxin neutralizing antibodies were absent in all treatment groups, and it is likely that the mice lack protection against lethal toxin and anthrax infection. Further studies are needed to optimize the formulation of DNA vaccines and increase the level of anti-lethal toxin antibodies and enhance their functionality.
authors.affiliation: Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WCIN1AX, UK.
authors.forename: Suzie
authors.initials: S
authors.lastname: Ribeiro
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: Rijpkema
authors.forename: Zarmina
authors.initials: Z
authors.lastname: Durrani
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Florence
mesh_terms: D000818:Animals; D000881:Anthrax / Q000628:therapy*; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects*; D000956:Antigens, Viral / Q000008:administration & dosage; D001408:Bacillus anthracis / Q000276:immunology; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D007109:Immunity / Q000187:drug effects*; D007114:Immunization; D019344:Lactic Acid / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D050091:Dendrimers; D004337:Drug Carriers; D011108:Polymers; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid