Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides

• Published in: Microbes and infection 2009-03, Vol.11 (3), p.352-360
• Main Authors: Lundqvist, Annika, Kubler-Kielb, Joanna, Teneberg, Susann, Ahlman, Karin, Lagergård, Teresa
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - isolation & purification; Adjuvants, Immunologic - pharmacology; administration & dosage; Animals; Annan medicinsk grundvetenskap; Antibodies; Antibodies, Bacterial - blood; Bacterial; Bacteriology; Biological and medical sciences; blood; Bovine; Cells; Cells, Cultured; chemistry; Cultured; Fundamental and applied biological sciences. Psychology; Haemophilus ducreyi; Haemophilus ducreyi - chemistry; Haemophilus ducreyi - immunology; Humans; IgG subclasses; Immunogenicity; Immunoglobulin G; Immunoglobulin G - blood; Immunologic; immunology; Inbred BALB C; Injections; Injections, Subcutaneous; isolation & purification; Knockout; Leukocytes; Leukocytes, Mononuclear - immunology; Lipid A; Lipooligosaccharide; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - immunology; Lipopolysaccharides - isolation & purification; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred BALB C; Mice, Knockout; Microbiology; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Miscellaneous; Mononuclear; Myeloid Differentiation Factor 88; Myeloid Differentiation Factor 88 - immunology; Other Basic Medicine; pharmacology; secretion; Serum Albumin; Serum Albumin, Bovine - immunology; Subcutaneous; Toll-Like Receptor 4; Toll-Like Receptor 4 - immunology; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - secretion
• ISSN: 1286-4579; 1769-714X; 1769-714X
• DOI: 10.1016/j.micinf.2008.12.014

Haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (HdLOS) that comprise 5–11 partially sialylated monosaccharides. Subcutaneous immunisation of mice with 5 μg of HdLOS purified from H. ducreyi strains 4438 and 7470 induced high levels of anti-HdLOS IgG. The antibody responses displayed T-cell-independent features, and were dependent upon Toll-like receptor 4/MyD88 signalling pathways as demonstrated using knockout mice. The immunogenicity of HdLOS was found to require the intact lipid A moiety. The specificity studies of the anti-HdLOS antibodies, as revealed by absorption studies, antibody detection in ELISA, and immune thin-layer chromatography, indicated that the majority of the anti-LOS antibodies were specific for the inner core of the HdLOS. Antibodies to HdLOS failed to inhibit LOS induction of TNF-α release from human mononuclear cells. The adjuvanticity of HdLOS7470 was assessed in BALB/c mice that were immunised with bovine serum albumin (BSA) with or without the addition of HdLOS. The addition of 5 μg HdLOS resulted in a 10-fold increase in the total anti-BSA IgG antibody level as estimated by ELISA. The highest increase was noted for IgG2b, which contrasted with the predominantly IgG1 subclass response to immunisation with BSA alone, indicating an immunomodulatory activity of the HdLOS.