Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously
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| Title: | Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously |
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| Authors: | Saupe, Falk, Reichel, Matthias, Huijbers, Elisabeth J M, Femel, Julia, Markgren, Per-Olof, Andersson, C Evalena, Deindl, Sebastian, Danielson, U Helena, Hellman, Lars T, Olsson, Anna-Karin |
| Source: | 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 2017, 'Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously', FASEB Journal, vol. 31, no. 3, pp. 1204-1214. https://doi.org/10.1096/fj.201600820R |
| Publisher Information: | Wiley, 2016. |
| Publication Year: | 2016 |
| Subject Terms: | Fish Proteins, 0301 basic medicine, Vaccines, Vaccines, Synthetic, Immunologic/genetics, Galectins, Antibody Affinity, Lampreys, Inbred C57BL, Galectins/genetics, Lampreys/immunology, Autoantigens, Synthetic/genetics, 12. Responsible consumption, 3. Good health, Mice, Inbred C57BL, Mice, 03 medical and health sciences, Autoantigens/immunology, Receptors, Animals, Fish Proteins/genetics, Receptors, Immunologic |
| Description: | 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-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. |
| Document Type: | Article |
| Language: | English |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201600820r |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/27993994 https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.201600820R http://www.diva-portal.org/smash/record.jsf?pid=diva2:1106512 https://www.fasebj.org/doi/full/10.1096/fj.201600820R https://europepmc.org/abstract/MED/27993994 https://www.ncbi.nlm.nih.gov/pubmed/27993994 https://research.vumc.nl/en/publications/development-of-a-novel-therapeutic-vaccine-carrier-that-sustains- https://research.vumc.nl/en/publications/c63a4ff4-fb20-4123-8b7d-8c6c44e39f4e |
| Rights: | Wiley Online Library User Agreement |
| Accession Number: | edsair.doi.dedup.....d9e4864bd13e52741c1b2f80dedc1a65 |
| Database: | OpenAIRE |
Nájsť tento článok vo Web of Science | 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 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-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. |
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| ISSN: | 15306860 08926638 |
| DOI: | 10.1096/fj.201600820r |