Bordetella pertussis fimbriae are effective carrier proteins in Neisseria meningitidis serogroup C conjugate vaccines

Reddin, K

doi:10.1016/s0928-8244(01)00254-1

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…A vaccine including this fusion protein may elicit protective immunity against many clinically important GBS strains, including almost all strains causing meningitis. The RibN-aN protein may also be suitable as carrier in a polysaccharide conjugate, allowing the development of a single vaccine that protects against different pathogens (Reddin et al, 2001;Lindahl et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Nonimmunodominant Regions Are Effective as Building Blocks in a Streptococcal Fusion Protein Vaccine

Stålhammar‐Carlemalm

Waldemarsson

Johnsson

et al. 2007

Cell Host & Microbe

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Identification of antigens that elicit protective immunity is essential for effective vaccine development. We investigated the related surface proteins of group B Streptococcus, Rib and alpha, as potential vaccine candidates. Paradoxically, nonimmunodominant regions proved to be of particular interest as vaccine components. Mouse antibodies elicited by Rib and alpha were directed almost exclusively against the C-terminal repeats and not against the N-terminal regions. However, a fusion protein derived from the nonimmunodominant N-terminal regions of Rib and alpha was much more immunogenic than one derived from the repeats and was immunogenic even without adjuvant. Moreover, antibodies to the N-terminal fusion protein protected against infection and inhibited bacterial invasion of epithelial cells. Similarly, the N-terminal region of Streptococcus pyogenes M22 protein, which is targeted by opsonic antibodies, is nonimmunodominant. These data indicate that nonimmunodominant regions of bacterial antigens could be valuable for vaccine development.

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Section: Discussionmentioning

confidence: 99%

Nonimmunodominant Regions Are Effective as Building Blocks in a Streptococcal Fusion Protein Vaccine

Stålhammar‐Carlemalm

Waldemarsson

Johnsson

et al. 2007

Cell Host & Microbe

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“…In this study we describe the generation of a new phoP meningococcal mutant derived from a serogroup C strain previously demonstrated to be virulent in the mouse (45), and we show that the phoP mutant is completely avirulent in the mouse model of infection. These results confirm that the PhoP-PhoQ system is involved in controlling virulence genes in the meningococcus.…”

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confidence: 93%

Infection with an Avirulent phoP Mutant of Neisseria meningitidis Confers Broad Cross-Reactive Immunity

et al. 2004

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Successful vaccines against serogroup A and C meningococcal strains have been developed, but current serogroup B vaccines provide protection against only a limited range of strains. The ideal meningococcal vaccine would provide cross-reactive immunity against the variety of strains that may be encountered in any community, but it is unclear whether the meningococcus possesses immune targets that have the necessary level of cross-reactivity. We have generated a phoP mutant of the meningococcus by allele exchange. PhoP is a component of a two-component regulatory system which in other bacteria is an important regulator of virulence gene expression. Inactivation of the PhoP-PhoQ system in Salmonella leads to avirulence, and phoP mutants have been shown to confer protection against virulent challenge. These mutants have been examined as potential live attenuated vaccines. We here show that a phoP mutant of the meningococcus is avirulent in a mouse model of infection. Moreover, infection of mice with the phoP mutant stimulated a bactericidal immune response that not only killed the infecting strain but also showed cross-reactive bactericidal activity against a range of strains with different serogroup, serotype, and serosubtyping antigens. Sera from the mutant-infected mice contained immunoglobulin G that bound to the surface of a range of meningococcal strains and mediated opsonophagocytosis of meningococci by human phagocytic cells. The meningococcal phoP mutant is thus a candidate live, attenuated vaccine strain and may also be used to identify cross-reactive protective antigens in the meningococcus.

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“…Antibodies to fimbriae can facilitate phagocytosis of bacteria [6,11]. Fimbrial conjugates have been used for the preparation of vaccines against experimental and natural diseases caused by E. coli , Neisseria gonorrhoeae , N. meningitidis , Bordetella pertussis , Pseudomonas aeruginosa , Haemophilus influenzae and Porphyromonas gingivalis [35–37]. The protective efficacy of fimbriae might be increased and extended by coupling with an epitope of broad specificity.…”

Section: Discussionmentioning

confidence: 99%

Major structural proteins of type 1 and type 3Klebsiellafimbriae are effective protein carriers and immunogens in conjugates as revealed from their immunochemical characterization

Witkowska

Mieszała²,

Gamian

et al. 2005

FEMS Immunology &Amp; Medical Microbiology

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Fimbriae are filamentous structures present on the cell surface of many bacteria, including genus Klebsiella. The use of fimbriae as protein carriers in conjugates may allow to formulate effective multivalent vaccines and suitable diagnostics. However, the evidences have been reported that fimbriae may enhance the inflammatory response. This prompted us to examine the degree of cytokine induction by the type 1 and type 3 Klebsiella fimbriae and their conjugates. Fimbriae were assessed as carrier proteins for Escherichia coli K12 endotoxin core oligosaccharide. MALDI-MS revealed the molecular mass of fimbrial monomer major protein, which was 15,847 Da for type 1 and 18,574 Da for type 3 fimbriae of Klebsiella. These two types of fimbriae were moderate inductors of IL-6 and interferon and almost inactive with regard to the stimulation of TNF when tested in human whole blood assay. Coupling of fimbriae with E. coli K12 core oligosaccharide gave immunogenic conjugates with respect to a saccharide ligand and protein carrier, although only 10% of the pilin monomers possessed the attached oligosaccharide. Rabbit antiserum reacted with a broad spectrum of lipopolysaccharides, as measured by ELISA and immunoblotting assays. The antibodies against glycoconjugates were bactericidal for the wild, S-type bacteria of some species. Regarding the induction of cytokines by conjugates only the TNF level was noticeably elevated. These results prompt for the practical use of fimbriae, as effective protein carriers for conjugates to obtain broad-spectrum antisera for diagnostic applications.

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Bordetella pertussis fimbriae are effective carrier proteins in Neisseria meningitidis serogroup C conjugate vaccines

Cited by 3 publications

References 21 publications

Nonimmunodominant Regions Are Effective as Building Blocks in a Streptococcal Fusion Protein Vaccine

Nonimmunodominant Regions Are Effective as Building Blocks in a Streptococcal Fusion Protein Vaccine

Infection with an Avirulent phoP Mutant of Neisseria meningitidis Confers Broad Cross-Reactive Immunity

Major structural proteins of type 1 and type 3Klebsiellafimbriae are effective protein carriers and immunogens in conjugates as revealed from their immunochemical characterization

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