Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens.
This report characterizes Vaxfectin, a novel cationic and neutral lipid formulation which enhances antibody responses when complexed with an antigen-encoding plasmid DNA (pDNA). In mice, intramuscular injection of Vaxfectin formulated with pDNA encoding influenza nucleoprotein (NP) increased antibody titers up to 20-fold, to levels that could not be reached with pDNA alone. As little as 1 microg of pDNA formulated with Vaxfectin per muscle resulted in higher anti-NP titers than that obtained with 25 microg naked pDNA. The antibody titers in animals injected with Vaxfectin-pDNA remained higher than in the naked pDNA controls for at least 9 months. The enhancement in antibody titers was dependent on the Vaxfectin dose and was accomplished without diminishing the strong anti-NP cytolytic T cell response typical of pDNA-based vaccines. In rabbits, complexing pDNA with Vaxfectin enhanced antibody titers up to 50-fold with needle and syringe injections and also augmented humoral responses when combined with a needle-free injection device. Vaxfectin did not facilitate transfection and/or increase synthesis of beta-galactosidase reporter protein in muscle tissue. ELISPOT assays performed on bone marrow cells from vaccinated mice showed that Vaxfectin produced a three- to five-fold increase in the number of NP-specific plasma cells. Thus, Vaxfectin should be a useful adjuvant for enhancing pDNA-based vaccinations.
Hartikka
J
J
Department of Cell Biology, Vical Incorporated, San Diego, CA 92121, USA.
Bozoukova
V
V
Ferrari
M
M
Sukhu
L
L
Enas
J
J
Sawdey
M
M
Wloch
M K
MK
Tonsky
K
K
Norman
J
J
Manthorpe
M
M
Wheeler
C J
CJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation / Q000187:drug effects*; D000956:Antigens, Viral / Q000235:genetics; D005260:Female; D017930:Genes, Reporter; D007700:Kinetics; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000378:metabolism; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011817:Rabbits; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D008055:Lipids; D009698:Nucleoproteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins