Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes.
Nucleic acid immunization is a novel vaccination technique to induce antigen-specific immune responses. We have developed expression cassettes for cell surface markers CD80 and CD86, two functionally related costimulatory molecules that play an important role in the induction of T cell-mediated immune responses. Coimmunization of these expression plasmids, along with plasmid DNA encoding for HIV-1 antigens, did not result in any significant change in the humoral response; however, we observed a dramatic increase in cytotoxic T-lymphocyte (CTL) induction as well as T-helper cell proliferation after the coadministration of CD86 genes. In contrast, coimmunization with a CD80 expression cassette resulted in a minor, but positive increase in T-helper cell or CTL responses. This strategy may be of value for the generation of rationally designed vaccines and immune therapeutics.
Kim
J J
JJ
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104, USA.
Bagarazzi
M L
ML
Trivedi
N
N
Hu
Y
Y
Kazahaya
K
K
Wilson
D M
DM
Ciccarelli
R
R
Chattergoon
M A
MA
Dang
K
K
Mahalingam
S
S
Chalian
A A
AA
Agadjanyan
M G
MG
Boyer
J D
JD
Wang
B
B
Weiner
D B
DB
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000235:genetics; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen; D001483:Base Sequence; D001709:Biotechnology; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D015202:Protein Engineering; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics* / Q000494:pharmacology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D017931:DNA Primers; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA