Intranasal administration of human immunodeficiency virus type-1 (HIV-1) DNA vaccine with interleukin-2 expression plasmid enhances cell-mediated immunity against HIV-1.
DNA vaccine against human immunodeficiency virus type-1 (HIV-1) can induce substantial levels of HIV-1-specific humoral and cell-mediated immunity. To develop more potent HIV-1 DNA vaccine formulations, we used a murine model to explore the immunomodulatory effects of an interleukin-2 (IL-2) expression plasmid on an HIV-1 DNA vaccine following intranasal administration of the combination. When the vaccine and expression plasmid were incorporated into cationic liposomes and administered to mice, the HIV-1-specific delayed-type hypersensitivity response and cytotoxic T lymphocyte activity were significantly increased. Restimulated immune lymphoid cells showed enhanced production of both IL-2 and interferon-gamma and reduced secretion of IL-4. The level of total antibody to HIV-1 antigen was not greatly changed by coadministration of the DNA vaccine and IL-2 expression plasmid. An analysis of serum HIV-1-specific IgG subclasses showed a significant drop in the IgG1/IgG2a ratio in the group that received the plasmid-vaccine combination. These results demonstrate that the IL-2 expression plasmid strongly enhances the HIV-1-specific immune response via activation of T helper type-1 cells.
Department of Bacteriology, Yokohama City University School of Medicine, Japan.
K Q
KQ
Xin
K
K
Hamajima
S
S
Sasaki
A
A
Honsho
T
T
Tsuji
N
N
Ishii
X R
XR
Cao
Y
Y
Lu
J
J
Fukushima
P
P
Shapshak
S
S
Kawamoto
K
K
Okuda
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage*; D005243:Feces / Q000737:chemistry; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007376:Interleukin-2; D019444:Vaccines, DNA