title: Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously.
abstract: With the aim to improve the efficacy of therapeutic vaccines that target self-antigens, we have developed a novel fusion protein vaccine on the basis of the C-terminal multimerizing end of the variable lymphocyte receptor B (VLRB), the Ig equivalent in jawless fishes. Recombinant vaccines were produced inEscherichia coliby fusing the VLRB sequence to 4 different cancer-associated target molecules. The anti-self-immune response generated in mice that were vaccinated with VLRB vaccines was compared with the response in mice that received vaccines that contained bacterial thioredoxin (TRX), previously identified as an efficient carrier. The anti-self-Abs were analyzed with respect to titers, binding properties, and duration of response. VLRB-vaccinated mice displayed a 2- to 10-fold increase in anti-self-Ab titers and a substantial decrease in Abs against the foreign part of the fusion protein compared with the response in TRX-vaccinated mice (P< 0.01). VLRB-generated Ab response had duration similar to the corresponding TRX-generated Abs, but displayed a higher diversity in binding characteristics. Of importance, VLRB vaccines could sustain an immune response against several targets simultaneously. VLRB vaccines fulfill several key criteria for an efficient therapeutic vaccine that targets self-antigens as a result of its small size, its multimerizing capacity, and nonexposed foreign sequences in the fusion protein.-Saupe, F., Reichel, M., Huijbers, E. J. M., Femel, J., Markgren, P.-O., Andersson, C. E., Deindl, S., Danielson, U. H., Hellman, L. T., Olsson, A.-K. Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Falk
authors.initials: F
authors.lastname: Saupe
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Reichel
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Elisabeth J M
authors.initials: EJ
authors.lastname: Huijbers
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Femel
authors.affiliation: Department of Chemistry-BMC, Biomedical Center, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Markgren
authors.affiliation: Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: C Evalena
authors.initials: CE
authors.lastname: Andersson
authors.affiliation: Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Deindl
authors.affiliation: Department of Chemistry-BMC, Biomedical Center, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: U Helena
authors.initials: UH
authors.lastname: Danielson
authors.affiliation: Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lars T
authors.initials: LT
authors.lastname: Hellman
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; anna-karin.olsson@imbim.uu.se.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Olsson
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D001324:Autoantigens / Q000276:immunology; D029941:Fish Proteins / Q000235:genetics / Q000276:immunology*; D037161:Galectins / Q000235:genetics / Q000276:immunology; D007798:Lampreys / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
chemical_list: D001324:Autoantigens; D029941:Fish Proteins; D037161:Galectins; D011971:Receptors, Immunologic; D014614:Vaccines, Synthetic
keywords: ED-A; ED-B; VLRB; cancer; tolerance