Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine

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DOIResolve DOI: http://doi.org/10.1073/pnas.1100782108
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TypeArticle
Journal titleProceedings of the National Academy of Sciences of the United States of America
ISSN0027-8424
Volume108
Issue10
Pages40874092; # of pages: 6
Subjectbacterium antibody; immunoglobulin G; immunoglobulin M; lipopolysaccharide; oligosaccharide; pertussis vaccine; trisaccharide; article; Bordetella bronchiseptica; Bordetella pertussis; enzyme linked immunosorbent assay; immunogenicity; microbial activity; mouse; nonhuman; priority journal; serology; Animals; Antibodies, Bacterial; Bordetella bronchiseptica; Bordetella pertussis; Carbohydrate Sequence; Electrophoresis, Polyacrylamide Gel; Female; Mice; Molecular Sequence Data; Oligosaccharides; Pertussis Vaccine; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Bordetella bronchiseptica; Bordetella pertussis; Mus; Negibacteria
AbstractPertussis 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.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21271308
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Record identifier707f5160-0302-4221-8757-f166f2c9f271
Record created2014-03-24
Record modified2016-05-09
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