Delivery of DNA HIV-1 vaccine to the liver induces high and long-lasting humoral immune responses.
The quality of immune responses induced by DNA vaccination depends on the site of DNA administration, the expression, and the properties of the encoded antigen. In the present study, we demonstrate that intravenous hydrodynamic HIV-1 envelope DNA injection resulted in high levels of expression of HIV-1 envelope antigen in the liver. When compared to the administration of DNA by i.n., i.d., i.m., and i.splenic routes, hydrodynamic vaccination induced, upon DNA boosting, levels of HIV-1 envelope-specific antibodies 40-fold higher than those elicited by the other routes tested. Hydrodynamic vaccination with 1 microg DNA induced higher humoral responses than 100 microg DNA given intramuscularly in the prime-boost regimen. High levels of envelope-specific IgG and IgA antibodies were induced in genital tract secretions after two doses of DNA followed by intranasal boosting with recombinant HIV-1 gp120 protein. Furthermore, two doses of 100 microg DNA generated interferon-gamma production in approximately 4.3+/-1.7% of CD8(+) splenocytes after in vitro stimulation with HIV-1 envelope peptides. These results demonstrate that DNA vaccines targeted to tissues with high proteosynthetic activity, such as the liver, results in enhanced immune responses.
Raska
Milan
M
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA. raskamil@uab.edu
Moldoveanu
Zina
Z
Novak
Jan
J
Hel
Zdenek
Z
Novak
Lea
L
Bozja
Jadranka
J
Compans
Richard W
RW
Yang
Chinglai
C
Mestecky
Jiri
J
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007117:Immunization, Secondary; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic; D014621:Vagina / Q000276:immunology
D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma