| 1. |
- Kubler-Kielb, Joanna, et al.
(author)
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Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine.
- 2011
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 108:10, s. 4087-92
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Journal article (peer-reviewed)abstract
- Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity.
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| 2. |
- Lundqvist, Annika, 1969, et al.
(author)
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Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides.
- 2009
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In: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1769-714X. ; 11:3, s. 352-60
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Journal article (peer-reviewed)abstract
- Haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (HdLOS) that comprise 5-11 partially sialylated monosaccharides. Subcutaneous immunisation of mice with 5 microg 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-alpha 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 microg 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.
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| 3. |
- Robbins, John B, et al.
(author)
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Pertussis vaccine: a critique.
- 2009
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In: The Pediatric infectious disease journal. - 0891-3668. ; 28:3, s. 237-41
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Journal article (peer-reviewed)abstract
- A critical level of serum IgG pertussis toxin antibody is both essential and sufficient to confer individual and herd immunity to pertussis. Monocomponent pertussis toxoid conferred such immunity in Sweden and in Denmark. We refute the notion that filamentous hemagglutinin, pertactin, and fimbriae add to the immunity conferred by pertussis toxoid and describe the artifact created when efficacy is estimated for multicomponent pertussis vaccines. Lastly, the genetically-inactivated mutant pertussis toxoid is safer, more immunogenic, and should be more effective than the current chemically-inactivated pertussis toxin.
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