Enhanced protective efficacy of a tuberculosis DNA vaccine by adsorption onto cationic PLG microparticles.
Immunization with plasmid DNA vectors represents a promising new approach to vaccination. It has been shown to elicit humoral and cellular immunity and protection in various infection models. Here, we assessed the immunogenicity and protective efficacy of a DNA vaccine vector encoding the antigen 85A (Ag85A) of Mycobacterium tuberculosis. Since intramuscular (i.m.) immunization with naked DNA requires considerable amounts of DNA in order to be effective, we evaluated a strategy to reduce the amount of DNA needed. To this end, we used Ag85A DNA adsorbed onto cationic poly(DL-lactide-co-glycolide) (PLG) microparticles and observed similar levels of protection against aerosol challenge in mice using doses of PLG-DNA two orders of magnitude lower than with naked DNA itself.
MPI for Infection Biology, Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany. mollenkopf@mpiib-berlin.mpg.de
Hans-Joachim
HJ
Mollenkopf
Guido
G
Dietrich
Joachim
J
Fensterle
Leander
L
Grode
Klaus-Dieter
KD
Diehl
Bernhard
B
Knapp
Manmohan
M
Singh
Derek T
DT
O'Hagan
Jeffrey B
JB
Ulmer
Stefan H E
SH
Kaufmann
D000327:Adsorption; D000818:Animals; D017931:DNA Primers; D016503:Drug Delivery Systems; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D013601:T-Lymphocytes / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use
D017931:DNA Primers; D011108:Polymers; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma