title: Enhancement of antibody responses by DNA immunization using expression vectors mediating efficient antigen secretion.
abstract: The immune responses elicited in mice, after intradermal (i.d.) immunization with plasmids encoding secreted or intracellular forms of HIV-1 nef, HIV-1 tat or C. pneumoniae omp2 proteins, respectively, were compared. To mediate secretion of these proteins the genes were fused to a heterologous signal sequence from murine heavy chain IgG. The nef- and omp2-specific antibody responses were dramatically increased when mice were inoculated with the plasmid encoding the secreted form of these proteins. In contrast, HIV-1 tat comprising an internal strong nuclear targeting sequence could not be induced to secretion and subsequently no enhanced antibody response was observed. Slight improvement of the HIV-1 nef antibody response was achieved after co-inoculation with a granulocyte-macrophage colony-stimulating factor (GM-CSF) expression vector. Further, nef-specific T-cell responses were induced after nef DNA injections, and were of Th1-like phenotype regardless of whether the nef protein was secreted or not. The system described in this study, using a plasmid vector with a strong heterologous signal sequence that mediate efficient antigen secretion in vivo, may have wide applicability for the induction of high antibody levels to normally non-secreted antigens.
authors.affiliation: Microbiology and Tumorbiology Center (MTC), Karolinska Institute, Box 280, 171 77, Stockholm, Sweden. cecilia.svanholm@mtc.ki.se
authors.forename: C
authors.initials: C
authors.lastname: Svanholm
authors.forename: L
authors.initials: L
authors.lastname: Bandholtz
authors.forename: A
authors.initials: A
authors.lastname: Lobell
authors.forename: H
authors.initials: H
authors.lastname: Wigzell
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000917:Antibody Formation; D000941:Antigens / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D015754:Genes, nef; D015756:Genes, tat; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007114:Immunization; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology*
chemical_list: D000907:Antibodies, Bacterial; D000941:Antigens; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D015483:HIV Antibodies; C063931:Omp2 protein, bacteria; D019444:Vaccines, DNA