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Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2017 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 31, no 3, 1204-1214 p.Article in journal (Refereed) Published
Abstract [en]

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 in Escherichia coli by 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-Abswere analyzed with respect to titers, binding properties, and duration of response. VLRB-vaccinatedmice 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-generatedAbs, 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.

Place, publisher, year, edition, pages
2017. Vol. 31, no 3, 1204-1214 p.
Keyword [en]
cancer, VLRB, tolerance, ED-A, ED-B
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-320668DOI: 10.1096/fj.201600820RISI: 000395671200032PubMedID: 27993994OAI: oai:DiVA.org:uu-320668DiVA: diva2:1106512
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2017-06-07 Created: 2017-06-07 Last updated: 2017-06-07Bibliographically approved

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Saupe, FalkHuijbers, Elisabeth J. M.Femel, JuliaMarkgren, Per-OlofDeindl, SebastianHellman, Lars T.Olsson, Anna-Karin

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Saupe, FalkHuijbers, Elisabeth J. M.Femel, JuliaMarkgren, Per-OlofDeindl, SebastianDanielson, U. HelenaHellman, Lars T.Olsson, Anna-Karin
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Department of Medical Biochemistry and MicrobiologyDepartment of Chemistry - BMCDepartment of Cell and Molecular BiologyScience for Life Laboratory, SciLifeLabMolecular Systems BiologyBiochemistry
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The FASEB Journal
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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