Induction of gp120-specific protective immune responses by genetic vaccination with linear polyethylenimine-plasmid complex.
The induction of IFN-gamma-secreting CD8+ T cells and neutralizing antibodies to HIV-1 are both key requirements for prevention of viral transmission and clearance of pathogenic HIV. Although DNA vaccination has been shown to induce both humoral and cellular immune responses against HIV antigens, the magnitude of the immune responses has always been disappointing. In this report, we analyze the ability of polyethylenimine (PEI)-DNA complex expressing an HIV-glycoprotein 120 (gp120) antigen (PEI-pgp120) to induce systemic CD8+ T cell and humoral responses to the gp120 antigen. The administration of PEI-plasmid complex resulted in rapid elevation of serum levels of IL-12 and IFN-gamma. Furthermore, a single administration of PEI-pgp120 complex elicits a number of gp120-specific CD8+ T cells 20 times higher than that elicited by three intramuscular injections of naked DNA. Interestingly, we found that systemic vaccination with PEI-pgp120 induced protective immune responses against both systemic and mucosal challenges with a recombinant vaccinia virus expressing a gp120 antigen. The data also demonstrated that the depletion of macrophages with liposome-encapsulated clodronate completely abolished gp120-specific cellular response. Overall, our results showed that a single administration of PEI-pgp120 complexes, eliciting strong immune responses, is an effective vaccination approach to generate protection against systemic and mucosal viral infections.
Garzón
Manolo Rodrigo
MR
Laboratory of Gene Therapy of Viral Hepatitis, Division of Hepatology and Gene Therapy, Clínica Universitaria/School of Medicine, Center for Applied Medical Research, University of Navarra, Pío XII 55, 31080 Pamplona, Spain.
Berraondo
Pedro
P
Crettaz
Julien
J
Ochoa
Laura
L
Vera
Maria
M
Lasarte
Juan Jose
JJ
Vales
Africa
A
Van Rooijen
Nico
N
Ruiz
Juan
J
Prieto
Jesús
J
Zulueta
Javier
J
González-Aseguinolaza
Gloria
G
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma; D011094:Polyethyleneimine