A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis.
Neutralization of the proinflammatory cytokine TNF-alpha by mAbs or soluble receptors represents an effective treatment for chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, or Crohn's disease. In this study, we describe a novel active immunization approach against TNF-alp...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1797057266172559360 |
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| author | Spohn, G Guler, R Johansen, P Keller, I Jacobs, M Beck, M Rohner, F Bauer, M Dietmeier, K Kündig, T Jennings, G Brombacher, F Bachmann, M |
| author_facet | Spohn, G Guler, R Johansen, P Keller, I Jacobs, M Beck, M Rohner, F Bauer, M Dietmeier, K Kündig, T Jennings, G Brombacher, F Bachmann, M |
| author_sort | Spohn, G |
| collection | OXFORD |
| description | Neutralization of the proinflammatory cytokine TNF-alpha by mAbs or soluble receptors represents an effective treatment for chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, or Crohn's disease. In this study, we describe a novel active immunization approach against TNF-alpha, which results in the induction of high titers of therapeutically active autoantibodies. Immunization of mice with virus-like particles of the bacteriophage Qbeta covalently linked to either the entire soluble TNF-alpha protein (Qbeta-C-TNF(1-156)) or a 20-aa peptide derived from its N terminus (Qbeta-C-TNF(4-23)) yielded specific Abs, which protected from clinical signs of inflammation in a murine model of rheumatoid arthritis. Whereas mice immunized with Qbeta-C-TNF(1-156) showed increased susceptibility to Listeria monocytogenes infection and enhanced reactivation of latent Mycobacterium tuberculosis, mice immunized with Qbeta-C-TNF(4-23) were not immunocompromised with respect to infection with these pathogens. This difference was attributed to recognition of both transmembrane and soluble TNF-alpha by Abs elicited by Qbeta-C-TNF(1-156), and a selective recognition of only soluble TNF-alpha by Abs raised by Qbeta-C-TNF(4-23). Thus, by specifically targeting soluble TNF-alpha, Qbeta-C-TNF(4-23) immunization has the potential to become an effective and safe therapy against inflammatory disorders, which might overcome the risk of opportunistic infections associated with the currently available TNF-alpha antagonists. |
| first_indexed | 2024-03-06T19:33:50Z |
| format | Journal article |
| id | oxford-uuid:1e5e11aa-abd0-4f41-993b-d66edbdc8cce |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:33:50Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:1e5e11aa-abd0-4f41-993b-d66edbdc8cce2022-03-26T11:16:01ZA virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1e5e11aa-abd0-4f41-993b-d66edbdc8cceEnglishSymplectic Elements at Oxford2007Spohn, GGuler, RJohansen, PKeller, IJacobs, MBeck, MRohner, FBauer, MDietmeier, KKündig, TJennings, GBrombacher, FBachmann, MNeutralization of the proinflammatory cytokine TNF-alpha by mAbs or soluble receptors represents an effective treatment for chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, or Crohn's disease. In this study, we describe a novel active immunization approach against TNF-alpha, which results in the induction of high titers of therapeutically active autoantibodies. Immunization of mice with virus-like particles of the bacteriophage Qbeta covalently linked to either the entire soluble TNF-alpha protein (Qbeta-C-TNF(1-156)) or a 20-aa peptide derived from its N terminus (Qbeta-C-TNF(4-23)) yielded specific Abs, which protected from clinical signs of inflammation in a murine model of rheumatoid arthritis. Whereas mice immunized with Qbeta-C-TNF(1-156) showed increased susceptibility to Listeria monocytogenes infection and enhanced reactivation of latent Mycobacterium tuberculosis, mice immunized with Qbeta-C-TNF(4-23) were not immunocompromised with respect to infection with these pathogens. This difference was attributed to recognition of both transmembrane and soluble TNF-alpha by Abs elicited by Qbeta-C-TNF(1-156), and a selective recognition of only soluble TNF-alpha by Abs raised by Qbeta-C-TNF(4-23). Thus, by specifically targeting soluble TNF-alpha, Qbeta-C-TNF(4-23) immunization has the potential to become an effective and safe therapy against inflammatory disorders, which might overcome the risk of opportunistic infections associated with the currently available TNF-alpha antagonists. |
| spellingShingle | Spohn, G Guler, R Johansen, P Keller, I Jacobs, M Beck, M Rohner, F Bauer, M Dietmeier, K Kündig, T Jennings, G Brombacher, F Bachmann, M A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. |
| title | A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. |
| title_full | A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. |
| title_fullStr | A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. |
| title_full_unstemmed | A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. |
| title_short | A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. |
| title_sort | virus like particle based vaccine selectively targeting soluble tnf alpha protects from arthritis without inducing reactivation of latent tuberculosis |
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