[Stimulation of synthesis of secretory immunoglobulin A in the lung by oral immunization: an approach with therapeutic relevance?].
Due to its strategic position on mucosal surfaces secretory immunoglobulin A (sIgA) is one of the first protective factors of the specific immune system against invading pathogens. As a factor of acquired immunity, the synthesis of sIgA can be modulated by various immunization strategies. Our experiments aimed at the enhancement of the sIgA pool in the lungs by oral immunization. As reported previously, commercially available LW 50020, an immunomodulator consisting of lysates of seven common pneumotropic pathogens, is effective in inducing significant IgA antibody responses in the lungs following oral immunization [1]. In the present study we developed new strategies to enhance this effect by encapsulating LW 50020 into microspheres and liposomes. Microspheres and liposomes with entrapped immunomodulator each enhanced the effect of soluble LW 50020 by about 45% and 90%, respectively. In addition, microsphere based immunization induced a significantly increased immunoglobulin G (IgG) response in the lungs. In further experiments we demonstrated that a similar effect could be achieved by administration of a high molecular weight conjugate of lipopolysaccharide from Klebsiella pneumoniae (LPS) and lipoteichoic acid from Streptococcus pyogenes (LTA). This conjugate enhanced the synthesis of IgA in the lungs by 45% and, furthermore, induced a significantly enhanced IgG response in the lungs, without any obvious toxic or pyrogenic side effects. This new conjugate possibly offers an opportunity to replace the complex immunomodulator LW 50020 by a less complex vaccine.
Kofler
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N
Institut für Allgemeine und Experimentelle Pathologie, Universität Innsbruck.
Wolf
H
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D016233:Immunotherapy, Active; D008081:Liposomes; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D004337:Drug Carriers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C078795:LW 50020; D008081:Liposomes