A role for liposomes in genetic vaccination.
Genetic immunization by the use of plasmid DNA encoding antigens from bacteria, viruses, protozoa and cancers has often led to protective humoral and cell-mediated immunity, and has some practical advantages over conventional vaccines. However, naked DNA vaccines can be degraded by nucleases in situ, are unable to target antigen presenting cells (APCs), and exhibit poor performance when administered by routes other than the intramuscular, all of which have reduced the value of the approach. We have been able to avoid DNA degradation and also target DNA to APCs by the use of liposomes as DNA vaccine carriers. Entrapment of plasmid DNA within the aqueous spaces of cationic liposomes is effected by a one step procedure which results in most of the DNA being incorporated into a freeze dried, ready to use preparation. Animal experiments have shown that immunization by the intramuscular or the subcutaneous route with liposome-entrapped plasmid DNA encoding the hepatitis B surface antigen leads to much greater humoral (IgG subclasses) and cell mediated (splenic IFN-gamma) immune responses than with naked DNA. In other experiments with a plasmid DNA encoding a model antigen (ovalbumin), a cytotoxic T lymphocyte (CTL) response was also observed. These results could be explained by the ability of liposomes to protect their DNA content from local nucleases and direct it to APCs in the lymph nodes draining the injected site.
Gregoriadis
Gregory
G
The School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK. gregoriadis@ulsop.ac.uk
Bacon
Andrew
A
Caparros-Wanderley
Wilson
W
McCormack
Brenda
B
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004333:Drug Administration Routes; D007111:Immunity, Cellular / Q000187:drug effects; D008081:Liposomes / Q000276:immunology; D051379:Mice; D010957:Plasmids; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D008081:Liposomes; D019444:Vaccines, DNA