Abstract • 36

Ribomunyl™ is a ribosomal vaccine constituted by proteoglycans from K. pneumoniae and by purified ribosomes from four respiratory pathogens. The proteoglycans from K. pneumoniae are well known to induce many in vitro and in vivo effects on the nonspecific immune response, including phagocytosis, chemotaxis, adhesion, and even natural killer (NK) lymphocyte activity. Incubation of human leukocytes in vitro with Ribomunyl™ stimulated the chemotactic activity of polymorphonuclear cells. Furthermore, the proteoglycans were potent in vitro stimulants of the oxidative burst of human neutrophils. Ribosomal preparations were found to increase the adhesive properties of polymorphonuclear cells in vitro, suggesting improved phagocytosis. Ribosomal preparations administered in vivo were first shown to prime alveolar macrophages to produce interleukin-1 (IL-1). Later, proteoglycans from K. pneumoniae were demonstrated to induce production of IL-8, monocyte chemotactic protein (MCP-1) and IL-6 by human monocytes in vitro. All these properties showed that ribosomal immunotherapy was able, by the proteoglycans it contains at least, to stimulate various aspects of the inflammatory response. In addition, membrane proteoglycans from K. pneumoniae were shown to stimulate NK cell activity in mice and in humans in vitro. The suppression of this effect by injecting anti-interferon-α (IFN-α) antibody to mice suggested that the NK activity was mediated by IFN-α. Recent experiments showed that proteoglycans were also able to induce the production of TGFβ from human B-lymphocytes, suggesting that this cytokine could induce the immunoglobulin switch from IgM to IgA in the mucosal tissues after oral administration of ribosomal immunotherapy.