title: Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: M L
authors.initials: ML
authors.lastname: Bagarazzi
authors.forename: N
authors.initials: N
authors.lastname: Trivedi
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: K
authors.initials: K
authors.lastname: Kazahaya
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Ciccarelli
authors.forename: M A
authors.initials: MA
authors.lastname: Chattergoon
authors.forename: K
authors.initials: K
authors.lastname: Dang
authors.forename: S
authors.initials: S
authors.lastname: Mahalingam
authors.forename: A A
authors.initials: AA
authors.lastname: Chalian
authors.forename: M G
authors.initials: MG
authors.lastname: Agadjanyan
authors.forename: J D
authors.initials: JD
authors.lastname: Boyer
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: 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*
chemical_list: 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