A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis.

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

Journal article

A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis.

Abstract:: 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.

Publication status:: Published

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APA Style

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. (2007). A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. Journal of Immunology, 178(11), 7450–7457.

MLA Style

Spohn, G, et al. “A Virus-like Particle-Based Vaccine Selectively Targeting Soluble TNF-Alpha Protects from Arthritis without Inducing Reactivation of Latent Tuberculosis.” Journal of Immunology, vol. 178, no. 11, 2007, pp. 7450–57.

Chicago Style

Spohn, G, R Guler, P Johansen, et al. 2007. “A Virus-like Particle-Based Vaccine Selectively Targeting Soluble TNF-Alpha Protects from Arthritis without Inducing Reactivation of Latent Tuberculosis.” Journal of Immunology 178 (11): 7450–57.
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