Improved cellular and humoral immune responses against Mycobacterium tuberculosis antigens after intramuscular DNA immunisation combined with muscle electroporation.
New delivery methods are needed to improve the efficiency of existing DNA vaccines. We have measured the immune response to Mycobacterium tuberculosis antigens following intramuscular DNA injection in combination with or without electroporation. Three to 6-fold increase in the number of antigen specific CD4(+) and CD8(+) T cells, measured by IFN-gamma-producing cells in an ELISPOT assay, was found in mice DNA injected and electroporated compared with non-electroporated mice. Similarly, 5 to 10-fold increase in antigen specific IgG1, IgG2a and IgG2b antibodies were found in an immunoglobulin subclass specific ELISA. A 100-fold reduction in DNA dose could be used without loss of efficiency when immunisation was combined with electroporation. A single injection of 1 microg of antigen 85b (ag85b) plasmid DNA was sufficient to elicit a higher and long lasting level of IgG2a antibodies against antigen 85B (Ag85B) compared to standard BCG vaccination. We conclude that DNA immunisation in combination with electroporation can significantly improve the immunogenicity of plasmid-based DNA vaccines.
Tollefsen
Stig
S
Institute of Immunology, University of Oslo, Norway.
Tjelle
Torunn
T
Schneider
Joerg
J
Harboe
Morten
M
Wiker
Harald
H
Hewinson
Glyn
G
Huygen
Kris
K
Mathiesen
Iacob
I
D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics*; D001500:BCG Vaccine / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018274:Electroporation; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018482:Muscle, Skeletal; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C060216:MPB70 protein, Mycobacterium bovis; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis