Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine

Martin, Sarah; Borrow, Raymond; Ley, Peter van der; Dawson, Maureen; Fox, Andrew; Cartwright, Keith

doi:10.1016/s0264-410x(00)00047-5

Cited by 62 publications

(45 citation statements)

References 25 publications

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“…Perhaps the most likely role for the FetA protein is as a component of OMV vaccines, along with other antigens such as PorA. These vaccines elicit bactericidal responses in people, including infants, but the immunity induced is strain-specific, probably as a consequence of antigenic diversity of their components (Martin et al, 2000). If FetA is to be used as a vaccine component consideration will have to be given to the conditions used for meningococcal growth.…”

Section: Discussionmentioning

confidence: 99%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 fetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VR). A nomenclature system for the peptides encoded by the VR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component.

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Section: Discussionmentioning

confidence: 99%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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“…31 A number of studies have shown that even small changes in the PorA sequence of target strains can abolish the bactericidal antibody response to meningococcal OMV-based vaccines. 32,33 Thus use of such meningococcal vaccines may be limited to interventions in outbreaks of disease caused by single clones of the organism such as that in Cuba in the 1980s 6 and the current outbreak in New Zealand, 34 which has lead to the concept of tailor-made OMV vaccines for the effective control of invasive meningococcal disease. 35 The mechanisms of immunity that confer cross-reactive protection in meningococcal disease are unclear; however, it is accepted that a key aim of immunization is to elicit a functional immune response, through bactericidal and/or opsonising antibody, capable of killing meningococcal strains from the range of serogroups, serotypes and serosubtypes that cause disease.…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

Characterization of the key antigenic components and pre-clinical immune responses to a meningococcal disease vaccine based onNeisseria lactamicaouter membrane vesicles

Finney¹,

Vaughan²,

Taylor³

et al. 2008

Human Vaccines

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“…Since group B polysaccharide is poorly immunogenic and has cross-reactivity with human neonatal neural tissue (13), a vaccine against group B disease has been developed based on OMPs. These vaccines have been shown to be safe and immunogenic in infants (8,17) and adults (18). Studies have suggested that OMP vaccines need to include multiple OMPs due to the diversity of the prevalence of OMPs in group B strains.…”

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confidence: 99%

Invasive Meningococcal Disease in Scotland, 1994 to 1999, with Emphasis on Group B Meningococcal Disease

et al. 2002

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A review was carried out on 774 invasive meningococcal isolates reported to the active meningococcal surveillance system in Scotland from 1994 to 1999. This showed that serogroups B (51.7%) and C (39.2%) caused the majority of disease. The six common PorB proteins (4, 1, 15, 2B, 12, and 21) and PorA proteins (serosubtypes) (P1.4, P1.15, P1.9, P1.14, P1.7, and P1.16) accounted for 50 and 51% of all group B isolates, respectively, during the study period.

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Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine

Cited by 62 publications

References 25 publications

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Characterization of the key antigenic components and pre-clinical immune responses to a meningococcal disease vaccine based onNeisseria lactamicaouter membrane vesicles

Invasive Meningococcal Disease in Scotland, 1994 to 1999, with Emphasis on Group B Meningococcal Disease

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