Clinical evaluation of a group B meningococcal N-propionylated polysaccharide conjugate vaccine in adult, male volunteers

Bruge, J.; Cam, Nancy Bouveret-Le; Danve, B.; Rougon, Geneviève; Schulz, Dominique

doi:10.1016/j.vaccine.2003.10.005

Cited by 84 publications

(35 citation statements)

References 54 publications

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Section: Ization After Careful Examination Of the Ev239mentioning

confidence: 99%

“…In 1981, it was reported that carbohydrates chemically resembling PSA are expressed during fetal development in humans (17). This observation suggested a rationalization to the poor response to PSA as the immune system being tolerant (17). Second, it raised the concern that a successful PSA-based vaccine could generate autoimmune reactions, limiting further studies of PSA-conjugate vaccines to animals (12,14).…”

Section: Ization After Careful Examination Of the Ev239mentioning

confidence: 99%

“…The finding that PSA-like antigens are expressed in healthy humans has restricted studies to animal models and, consequently, hampered the use of PSA as vaccine component (12)(13)(14)(15)(16). Efforts to obtain vaccines aimed at PSA but based on alternative components have been unsuccessful (17).…”

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confidence: 99%

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Extracellular structure of polysialic acid explored by on cell solution NMR

Azurmendi

Vionnet

Wrightson

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The capsular polysaccharide of the pathogens Neisseria meningitidis serogroup B and of Escherichia coli K1, ␣(2 3 8) polysialic acid (PSA), is unusual, because when injected into adult humans, it generates little or no antibody. In contrast, people infected with these pathogens generate specific serum antibodies. A structural study on cells is used to address this anomaly by characterizing antigen structures in vivo. We introduce on cell multidimensional solution NMR spectroscopy for direct observation of PSA on E. coli bacteria. Using 13 C, 15 N-labeled PSA, we applied a combination of heteronuclear NMR methods, such as heteronuclear single quantum coherence, HNCA, and HNCO, in vivo. Analysis reveals that free and cell-bound PSA are structurally similar, indicating that the poor immunogenicity of PSA is not due to major structural differences between cells and purified PSA. The 13 C linewidths of PSA on cells are 2 to 3 times larger than the corresponding ones in free PSA. The possible implications of the differences between free and on cell PSA are discussed. In addition, we demonstrate the suitability of the method for in vivo kinetic studies.carbohydrate structure ͉ isotopically labeled carbohydrates ͉ in vivo kinetics ͉ triple resonance NMR

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Section: Ization After Careful Examination Of the Ev239mentioning

confidence: 99%

Section: Ization After Careful Examination Of the Ev239mentioning

confidence: 99%

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Extracellular structure of polysialic acid explored by on cell solution NMR

Azurmendi

Vionnet

Wrightson

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Unfortunately, the capsular polysaccharide of serogroup B is poorly immunogenic, presumably due to its structural homology to polysialic acid on human neural cells (10)(11)(12). Efforts to develop vaccines based on the N. meningitidis serogroup B (MnB) capsular polysaccharide have failed (13). The lack of an effective MnB vaccine that provides broad coverage is reflected in the current meningococcal disease incidence.…”

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confidence: 99%

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

McNeil

Zagursky

Lin

et al. 2013

Microbiol Mol Biol Rev

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SUMMARY Neisseria meningitidis is a Gram-negative microorganism that exists exclusively in humans and can cause devastating invasive disease. Although capsular polysaccharide-based vaccines against serogroups A, C, Y, and W135 are widely available, the pathway to a broadly protective vaccine against serogroup B has been more complex. The last 11 years has seen the discovery and development of the N. meningitidis serogroup B (MnB) outer membrane protein factor H binding protein (fHBP) as a vaccine component. Since the initial discovery of fHBP, a tremendous amount of work has accumulated on the diversity, structure, and regulation of this important protein. fHBP has proved to be a virulence factor for N. meningitidis and a target for functional bactericidal antibodies. fHBP is critical for survival of meningococci in the human host, as it is responsible for the primary interaction with human factor H (fH). Binding of hfH by the meningococcus serves to downregulate the host alternative complement pathway and helps the organism evade host innate immunity. Preclinical studies have shown that an fHBP-based vaccine can elicit serum bactericidal antibodies capable of killing MnB, and the vaccine has shown very encouraging results in human clinical trials. This report reviews our current knowledge of fHBP. In particular, we discuss the recent advances in our understanding of fHBP, its importance to N. meningitidis , and its potential role as a vaccine for preventing MnB disease.

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“…2 Vaccines based on the serogroup B capsule have been poorly immunogenic and have failed to elicit serum bactericidal antibodies in clinical studies. 3,4 Serum bactericidal activity (SBA) against meningococcal strains has been considered the hallmark for estimating protection against meningococcal disease, and the absence of SBA following immunization with capsular B polysaccharide has been interpreted as a failure for this vaccine approach. The low immunogenicity is likely to be due to the structural homology between B polysaccharide and carbohydrate residues present in human tissue leading to immune tolerance.…”

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confidence: 99%