Cholera Toxin B Subunit as Transmucosal Carrier‐Delivery and Immunomodulating System for Induction of Antiinfectious and Antipathological Immunitya

Czerkinsky, Cécil; Sun, Jiabin; Lebens, Michael; Li, Bin-Ling; Rask, Carola; Lindblad, Marianne; Holmgren, Jan

doi:10.1111/j.1749-6632.1996.tb21127.x

Cited by 35 publications

(16 citation statements)

References 25 publications

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“…Previous work from this laboratory has indicated that oral administration of minute doses of foreign as well as self antigens coupled to the nontoxic, mucosabinding molecule CTB can modulate peripheral T cell reactivity to the conjugated antigen, in naïve as well as in systemically sensitized animals (18). The data presented herein further extend our previous work by demonstrating that targeting the autoantigen type II collagen to the nasal mucosa-associated lymphoid tissue by chemical linking to CTB not only reduces the severity of disease when the treatment is started at the preclinical phase, but is also efficient in preventing disease progression in mice with recent-onset arthritis.…”

Section: Discussionmentioning

confidence: 99%

Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine

Tarkowski

Sun

Holmdahl

et al. 1999

Arthritis & Rheumatism

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Objective. To assess the efficacy of intranasal administration of microgram amounts of type II collagen (CII) coupled to cholera toxin B subunit (CTB) with respect to the development of collagen-induced arthritis, even when given after the onset of clinically evident arthropathy.Methods. DBA/1 mice were immunized with CII to induce arthritis and were subsequently treated with CTB-CII, CTB-conjugated ovalbumin, or CII alone. The incidence and severity of arthritis were assessed clinically and histologically.Results. Treatment with CTB-CII conjugate effectively suppressed leukocyte infiltration into the synovium and prevented bone erosion. Comparable doses of unconjugated CII administered by the same route were relatively ineffective. Protection with nasal CTB-CII vaccine was associated with decreased production of interleukin-4 (IL-4), IL-6, and interferon-␥ and with reduced CII-specific IgG1 and IgG2a antibody responses in regional lymph nodes.Conclusion. Nasal treatment with CTB-CII appears to result in decreased peripheral Th1 and Th2 responses to collagen. These results suggest that intranasal vaccination with CTB-CII may offer an effective immunotherapeutic means for the control of chronic polyarthritis.

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Section: Discussionmentioning

confidence: 99%

Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine

Tarkowski

Sun

Holmdahl

et al. 1999

Arthritis & Rheumatism

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“…The carrier used in this study, CTB, binds to the cell surface monosialoganglioside GM1 (Cuatrecasas, 1973;Svennerholm, 1976;Czerkinsky et al, 1996), which is present in high concentrations in oligodendrocyte myelin (Yu and Iqbal, 1979;Cochran et al, 1982) and astrocytes (Byrne et al, 1988). Intrathecal injection of CTB-Sap resulted in large-scale removal of oligodendrocytes and astrocytes, creating optimal conditions for Schwann cells to migrate in and myelinate the spinal cord.…”

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confidence: 99%

Schwann Cells Are Removed from the Spinal Cord after Effecting Recovery from Paraplegia

et al. 2000

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Remyelination of the CNS is necessary to restore neural function in a number of demyelinating conditions. Schwann cells, the myelinating cells of the periphery, are candidates for this purpose because they have more robust regenerative properties than their central homologs, the oligodendrocytes. Although the ability of Schwann cells to remyelinate the CNS has been demonstrated, their capacity to enter the adult spinal cord in large numbers and effect functional recovery remains uncertain. We used cholera toxin B-subunit conjugated to saporin to demyelinate the rat lumbar spinal cord, remove macroglia, and produce paraplegia. After the removal of oligodendrocyte and astrocyte debris by invading macrophages, there was a spontaneous entry of Schwann cells into the spinal cord, along with axonal remyelination and concomitant functional recovery from paraplegia occurring within 75 d. The Schwann cells appeared to enter the dorsal funiculi via the dorsal root entry zone and the lateral funiculi via rootlets that had become adherent to the lateral spinal cord after the inflammation. In the following weeks, Schwann cell myelin surrounding central axons was progressively replaced by oligodendrocyte myelin without lapse in motor function. Our results show that endogenous Schwann cells can reverse a severe neurological deficit caused by CNS demyelination and enable later oligodendrocyte remyelination.

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“…CTB given simultaneously with a variety of antigens orally has been shown to enhance oral tolerance, to inhibit ongoing disease, and to lower the dose of antigen required to achieve tolerance [147][148][149][150]. These studies indicate that CTB could potentially improve oral tolerance in humans by requiring a lower dose of oral antigen as well as by improving the efficacy of tolerance initiated during chronic disease.…”

Section: Mucosal Adjuvantsmentioning

confidence: 92%

Oral tolerance in the treatment of inflammatory autoimmune diseases

Wardrop

1999

Inflamm. res.

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Oral tolerance refers to the oral administration of protein antigens, which induces a state of systemic nonresponsiveness specific for the fed antigen. This method of inducing immune non-responsiveness has been applied to the prevention and treatment of experimental animal models of autoimmune disease. Extensive research in this area over the past ten years has led to the conclusion that two mechanisms are operative in the mediation of oral tolerance--active suppression and clonal anergy/deletion. A number of factors have been identified that determine which mechanism of tolerance is operative--antigen dose, antigen form, and the timing of antigen administration. Work from these animal models has recently been extended into human clinical trials of multiple sclerosis, rheumatoid arthritis, diabetes, uveitis, and allergy, with differing degrees of success. In this review, a discussion is provided of the animal model systems where oral tolerance has been applied and the clinical trials where an oral tolerization approach has been attempted. Moreover, recent mechanistic studies are reviewed and a model proposed for the induction of oral tolerance.

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Cholera Toxin B Subunit as Transmucosal Carrier‐Delivery and Immunomodulating System for Induction of Antiinfectious and Antipathological Immunitya

Cited by 35 publications

References 25 publications

Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine

Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine

Schwann Cells Are Removed from the Spinal Cord after Effecting Recovery from Paraplegia

Oral tolerance in the treatment of inflammatory autoimmune diseases

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