Engineering DNA vaccines via co-delivery of co-stimulatory molecule genes.
DNA immunization has been investigated as a potential immunization strategy against infectious diseases and cancer. To enhance a DNA vaccine's ability to induce CTL response in vivo, we co-administered CD80 and CD86 expression cassettes along with HIV-1 immunogens. This manipulation resulted in a dramatic increase in MHC class I-restricted and CD8+ T-cell-dependent CTL responses in both mice and chimpanzees. This strategy of engineering vaccine producing cells to be more efficient T-cell activators could be an important tool for optimizing antigen-specific T-cell-mediated immune responses in the pursuit of more rationally designed vaccines and immune therapies.
Kim
J J
JJ
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104, USA.
Nottingham
L K
LK
Wilson
D M
DM
Bagarazzi
M L
ML
Tsai
A
A
Morrison
L D
LD
Javadian
A
A
Chalian
A A
AA
Agadjanyan
M G
MG
Weiner
D B
DB
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D051940:B7-2 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018076:DNA, Complementary; D000939:Epitopes; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D008222:Lymphokines; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA