Active immunization against murine TNFα peptides in mice: generation of endogenous antibodies cross-reacting with the native cytokine and in vivo protection

Capini, Christelle; Bertin-Maghit, Sebastien; Bessis, Natacha; Haumont, Philippe; Bernier, Emilie; Muel, E. G.; Laborie, Marion; Autin, Ludovic; Paturance, Sébastien; Chomilier, Jacques; Boissier, Marie Christophe; Briand, Jean‐Paul; Muller, S.; Cavaillon, Jean‐Marc; Therwath, Amu; Zagury, Jean‐François

doi:10.1016/j.vaccine.2004.01.064

Cited by 29 publications

(12 citation statements)

References 31 publications

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“…Similar results have been seen within other animal models with anti-cytokine vaccinations against TNFα, IL-1β, or IL-23 [6][7][8]. A small phase IIa trial of vaccination against TNFα has already been completed in humans, with successful development of anti-TNFα antibodies.…”

Section: Vaccinationsupporting

confidence: 77%

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

Middleton¹

2012

J Clin Cell Immunol

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Rheumatoid arthritis is a common, well studied autoimmune disease characterized by a loss of self-tolerance. Current therapies have significantly advanced the successful treatment of the disease, but have been unsuccessful for a large number of patients. Furthermore, they have failed to induce long term medication free remission because they target a consequence of the disease, not the origins of a dis-regulated immune system. Current research is now focused on finding ways to correct and restore the balance of the immune system rather than just suppress it. The scientific foundations for a number of potential approaches to restoring immune tolerance already have been laid. This paper reviews a number of proposed targets for immunotherapy including vaccinations, shifting from Th1 to Th2 responses, molecules that promote the resolution of inflammation, tolerogenic dendritic cells, mesenchymal stem cells, and T regulatory cells. These strategies will hopefully allow a closer approach to a "cure" for this potentially devastating disease.

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Section: Vaccinationsupporting

confidence: 77%

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

Middleton¹

2012

J Clin Cell Immunol

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“…This is of particular concern when this strategy is used in humans. Cytokine peptide-based vaccines are currently under development; however, these vaccines use inappropriate carrier proteins such as keyhole limpet hemocyanin (32). As these vaccines are not virus-like particles, their antigenicity is low, requiring strong adjuvants, such as complete Freund adjuvant, to elicit high titers of antibodies to the target cytokine.…”

Section: Discussionmentioning

confidence: 99%

Targeting IL-12/IL-23 by Employing a p40 Peptide-Based Vaccine Ameliorates TNBS-Induced Acute and Chronic Murine Colitis

Guan

Hillman

et al. 2011

Mol Med

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Interleukin (IL)-12 and IL-23 both share the p40 subunit and are key cytokines in the pathogenesis of Crohn's disease. Previously, we have developed and identified three mouse p40 peptide-based and virus-like particle vaccines. Here, we evaluated the effects and immune mechanisms of the optimal vaccine in downregulating intestinal inflammation in murine acute and chronic colitis, induced by intrarectal administrations of trinitrobenzene sulfonic acid (TNBS). Mice were injected subcutaneously with vaccine, vaccine carrier or saline three times, and then intrarectally administered TNBS weekly for 2 wks (acute colitis) or 7 wks (chronic colitis). The severity of colitis was evaluated by body weight, histology and collagen and cytokine levels in colon tissue. Th1 and Th17 cells in mesenteric lymph nodes (MLN) were determined. Our results showed the vaccine induced high level and long-lasting specific IgG antibodies to p40, IL-12 and IL-23. After administrations of TNBS, vaccinated mice had significantly less body weight loss and a significant decrease of inflammatory scores, collagen deposition and expression of p40, IL-12, IL-23, IL-17, TNF, iNOS and Bcl-2 in colon tissues, compared with carrier and saline groups. Moreover, vaccinated mice exhibited a trend to lower percentages of Th1 cells in acute colitis and of Th17 cells in chronic colitis in MLN than in controls. In summary, administration of the vaccine induced specific antibodies to IL-12 and IL-23, which was associated with improvement of intestinal inflammation and fibrosis. This suggests that the vaccine may provide a potential approach for the long-term treatment of Crohn's disease.

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“…Anti-cytokine vaccination as a therapeutic principle is appealing [43][44][45][46][47][48][49][50][51][52][53][54][55][56]: (i) It is simple and inexpensive (the basis of good clinical compliance); (ii) it might induce a profound anti-cytokine autoantibody response after a few injections; (iii) the endogenously produced antibodies are able to activate, various Fc dependent effector mechanisms and hence, effectively clear cytokine containing immune complexes (which might be difficult with passively transferred monoclonal antibodies [57,58]); (iv) the vaccine is apparently well tolerated (considered by no acute side effects of the vaccine [12,13] and the fact that high-titered cytokine autoantibodies are spontaneously produced by apparently healthy individuals [2,7,37,40]). …”

Section: Discussionmentioning

confidence: 99%

Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

Galle

Jensen

Andersson

et al. 2007

International Immunopharmacology

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Active immunization against murine TNFα peptides in mice: generation of endogenous antibodies cross-reacting with the native cytokine and in vivo protection

Cited by 29 publications

References 31 publications

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

Targeting IL-12/IL-23 by Employing a p40 Peptide-Based Vaccine Ameliorates TNBS-Induced Acute and Chronic Murine Colitis

Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

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