Multigene/multisubtype HIV-1 vaccine induces potent cellular and humoral immune responses by needle-free intradermal delivery.
Gene vaccination encounters problems different from those of gene therapy since both a short half-life of the gene and a strong immune response to the gene product are desirable. We have evaluated a DNA vaccine consisting of seven plasmids encoding nine HIV-1 proteins. Using a needle-free delivery device, the Biojector, together with recombinant mouse GM-CSF, this vaccine induced strong gp160 Env- and p24 Gag-specific cellular and humoral immune responses in mice. The rGM-CSF was crucial for inducing both antibodies and antigen-specific CD8(+) T cell responses against both gp160 and p24. A GMP-produced lot of this vaccine, intended for human use, was delivered intradermally or intramuscularly into BALB/c mice at a GLP-accredited animal facility. This vaccine induced strong cellular responses independent of the route of immunization; moreover, no signs of toxicity were detected after histopathological examination of various tissues. Overall, the results indicate that the intradermal delivery of multigene/multisubtype HIV DNA in combination with recombinant GM-CSF is a safe and efficacious strategy for inducing high levels of specific CD8(+) T cells and unusually high titers of antibodies. This vaccine has been approved by the Swedish Medicinal Products Agency and is currently in a Phase I clinical trial.
Bråve
Andreas
A
Swedish Institute for Infectious Disease Control, 171 82 Stockholm, Sweden. andreas.brave@smi.ki.se
Ljungberg
Karl
K
Boberg
Andreas
A
Rollman
Erik
E
Isaguliants
Maria
M
Lundgren
Björn
B
Blomberg
Pontus
P
Hinkula
Jorma
J
Wahren
Britta
B
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D015483:HIV Antibodies / Q000737:chemistry; D016655:HIV Core Protein p24 / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007271:Injections, Intradermal / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015233:Models, Statistical; D019444:Vaccines, DNA / Q000008:administration & dosage*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D019302:HIV Envelope Protein gp160; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA