Carbohydrate‐based particles: a new adjuvant for allergen‐specific immunotherapy

Abstract

Summary The occurrence of systemic anaphylactic side‐effects in the course of allergen‐specific immunotherapy has been strongly reduced by the adsorption of allergens to aluminium hydroxide, the most frequently used adjuvant in humans. Using the major timothy grass pollen allergen, Phl p 5b, in its recombinant form for immunization of mice, we demonstrate that carbohydrate‐based particles (CBP) exhibit several potential advantages over aluminium‐hydroxide as adjuvant for immunotherapy. Similar to alum‐bound rPhl p 5b, CBP‐bound rPhl p 5b induced a stronger antibody and cytokine response than unbound rPhl p 5b after subcutaneous injection in mice. The antibodies induced by CBP‐bound rPhl p 5b, exhibited potentially beneficial activities as they cross‐reacted with group 5 allergens from five other grass species and inhibited the binding of grass pollen allergic patients IgE to Phl p 5b. Alum‐bound rPhl p 5b induced a preferential allergen‐specific Th2‐response characterized by high immunoglobulin G1 (IgG1) antibody levels and elevated interleukin (IL)‐4 and IL‐5 production in cultured splenocytes. By contrast, CBP‐bound rPhl p 5b, but not rPhl p 5b alone or coadministered with CBP, induced a mixed allergen‐specific T helper 1 (Th1)/Th2 immune response characterized by the additional production of allergen‐specific IgG2a/b antibody responses and elevated interferon‐γ production. Conjugation of rPhl p 5b to CBP yielded a stable vaccine formulation with preserved immunogenic features of the allergen and, in contrast to alum, induced no granulomatous tissue reactions. Based on these results, CBP is suggested as a potentially useful adjuvant for specific immunotherapy of IgE‐mediated allergies.

The Major Cat Allergen, Fel d 1, in Diagnosis and Therapy

“…The rational for this approach is that the particles carrying large amounts of allergens should be phagocytosed by APCs, which will present the allergen-derived peptide-major histocompatibility complex II complexes at high density on the cell surface and exert immunomodulatory effects on allergen-specific T cells. In an initial study, it was shown that the particles, referred to as carbohydrate-based particles (CBP), exhibited beneficial properties for ASIT application when tested in vivo in naïve mice [83]. We then covalently coupled rFel d 1 to the particles (CBP-Fel d 1) and investigated the effect on human monocyte-derived dendritic cells [84].…”

Aktueller Stand der spezifischen Immuntherapie mit Tierepithelien

“…So entwickelten Schmitz [31]. Damit sollen die Partikel, die große Mengen von Allergen tragen, von Antigenpräsentierenden Zellen phagozytiert werden und über die Präsentation an der Zelloberfläche immunmodulatorische Effekte auf allergenspezifische T-Zellen auslösen [31].…”

“…So entwickelten Schmitz [31]. Damit sollen die Partikel, die große Mengen von Allergen tragen, von Antigenpräsentierenden Zellen phagozytiert werden und über die Präsentation an der Zelloberfläche immunmodulatorische Effekte auf allergenspezifische T-Zellen auslösen [31]. Im Mausmodell für Katzenallergie konnte diese Karbohydrat-basierte Partikeltherapie erfolgreich zur Behandlung der allergischen Atemwegsentzün-dung eingesetzt werden [32], wobei Daten zur Anwendung beim Menschen derzeit nicht vorliegen.…”

Nuevos esquemas de inmunoterapia específicas con alérgenos

“…La administración del alérgeno recombinante Phl p 5b unido covalentemente a partículas de sefarosa de 2 µm en ratones, indujo la producción de anticuerpos IgG 2 bloqueadores y una fuerte respuesta Th1. Aunque esta preparación también indujo la secreción de citocinas del perfil Th2, no provocó la formación de lesiones en la piel de los animales, como sí lo hizo el alérgeno solo o mezclado con hidróxido de aluminio (66).…”