Vaccine prevention of meningococcal disease, coming soon?

Morley, Sarah L.; Pollard, Andrew J.

doi:10.1016/s0264-410x(01)00410-8

Cited by 109 publications

(81 citation statements)

References 162 publications

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“…Vaccines based on capsular polysaccharide of the meningococcus are effective for protecting against serogroup A and C disease but provide only short-lived immunity (40). A conjugated serogroup C polysaccharide vaccine has recently been introduced in the United Kingdom, and its introduction has been associated with a dramatic reduction of serogroup C meningococcal disease (5).…”

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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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“…Since the serogroup B polysaccharide is poorly immunogenic in humans, attention has focused on the meningococcal OMPs. However, many OMPs are subject to antigenic variation, and although OMP-based vaccines have been developed, they give only limited immunity against genetically diverse meningococcal strains (11,40).…”

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

et al. 2004

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“…Characterization of meningococci according to serogroup is important given that most available meningococcal vaccines are capsular polysaccharide based (18). The exact effects of widespread immunization as far as inducing changes in the population structure of meningococci are unknown, but it is likely to affect the phenomenon of capsule switching and also to select for strains of serogroups previously considered to be of limited pathogenicity, such as serogroups 29E, X, and Z (20,24).…”

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PCR-Based Assay for Detection of Neisseria meningitidis Capsular Serogroups 29E, X, and Z

2004

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“…Current research into vaccine candidates suitable for the prevention of meningitis caused by serogroup B meningococci has focused on outer-membrane proteins (OMPs) and lipo-oligosaccharides (LOSs), either purified or naturally incorporated into outer-membrane vesicles (OMVs) (Morley & Pollard, 2001). The high antigenic variability of many OMPs limits the efficacy of singleprotein vaccines, and vaccines based on OMVs that contain all of the outer-membrane antigens in their native conformations have failed to induce cross-protection due to the immune dominance of PorA, the serosubtyping antigen, which presents a high degree of variability (Rosenqvist et al, 1995;Tappero et al, 1999;.…”

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A cross-reactive neisserial antigen encoded by the NMB0035 locus shows high sequence conservation but variable surface accessibility

Arenas

Abel

Sánchez

et al. 2008

Journal of Medical Microbiology

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The meningococcal NMB0035 locus encodes a 47 kDa outer-membrane protein that is highly conserved antigenically, and is able to induce antibodies during infection and bactericidal responses in vitro. This study analysed the surface exposure of this protein using specific antibodies in flow cytometry assays and determined its nucleotide sequence in 33 Neisseria strains. Genomic analyses revealed no significant differences in the nucleotide or amino acid sequences, but flow cytometry showed that surface accessibility was highly variable among the strains. These results suggest that masking by and/or association with lipo-oligosaccharides or other membrane molecules can be crucial for antigen accessibility, which must be thoroughly analysed in new vaccine candidates.

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Vaccine prevention of meningococcal disease, coming soon?

Cited by 109 publications

References 162 publications

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

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

PCR-Based Assay for Detection of Neisseria meningitidis Capsular Serogroups 29E, X, and Z

A cross-reactive neisserial antigen encoded by the NMB0035 locus shows high sequence conservation but variable surface accessibility

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