Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA.
Particle-mediated (gene gun) DNA transfer to the epidermis was evaluated for its ability to elicit humoral and cytotoxic T lymphocyte responses using decreasing quantities of plasmid DNA-based antigen expression vectors. Using plasmids encoding human growth hormone, human alpha-1-antitrypsin, and influenza virus nucleoprotein, strong immune responses were observed in mice following immunization with as little as 16 ng of DNA using an electric discharge gene delivery system. Significant antibody titers were observed against these antigens following a primary immunization, with responses rising dramatically following a boost. Increasing the DNA dose above 16 ng per immunization had little beneficial effect. In contrast to particle-mediated DNA delivery, intramuscular or intradermal inoculation required greater than 5000-fold more DNA to achieve comparable results. Data are also presented demonstrating that a simple, hand-held version of the Accell DNA delivery system, employing compressed helium as the particle motive force, achieves immune responses comparable to the traditional electric discharge device.
Pertmer
T M
TM
Agracetus, Inc., Middleton, WI 53562, USA.
Eisenbraun
M D
MD
McCabe
D
D
Prayaga
S K
SK
Fuller
D H
DH
Haynes
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D004279:DNA, Viral / Q000008:administration & dosage* / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004817:Epidermis; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology*; D013006:Growth Hormone / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D004279:DNA, Viral; D007074:Immunoglobulin G; D000515:alpha 1-Antitrypsin; D013006:Growth Hormone