Influence of serogroup B meningococcal vaccine antigens on growth and survival of the meningococcus in vitro and in ex vivo and in vivo models of infection

Seib, Kate L.; Oriente, Francesca; Adu‐Bobie, Jeannette; Montanari, P.; Ferlicca, Francesca; Giuliani, Marzia M.; Rappuoli, Rino; Pizza, Mariagrazia; Delany, Isabel

doi:10.1016/j.vaccine.2009.12.082

Cited by 33 publications

(42 citation statements)

References 42 publications

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“…Accordingly, a GNA2091 mutant was reported previously to display increased sensitivity toward SDS and Tween, suggesting infringement of the OM barrier function (26). Similarly, inactivation of the GNA2091 homolog YraP of E. coli resulted in an SDS-sensitive phenotype (16).…”

Section: Discussionmentioning

confidence: 89%

Involvement of Neisseria meningitidis Lipoprotein GNA2091 in the Assembly of a Subset of Outer Membrane Proteins

Bos

Grijpstra

Boxtel

et al. 2014

Journal of Biological Chemistry

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Background: Outer membrane protein assembly is an incompletely understood process in Gram-negative bacteria. Results: A Neisseria meningitidis mutant lacking the lipoprotein GNA2091 is affected in growth and accumulates unassembled outer membrane proteins. Conclusion:We identified a novel component involved in outer membrane biogenesis. Significance: Our findings contribute to the understanding of a fundamental process occurring in Gram-negative bacteria.

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Section: Discussionmentioning

confidence: 89%

Involvement of Neisseria meningitidis Lipoprotein GNA2091 in the Assembly of a Subset of Outer Membrane Proteins

Bos

Grijpstra

Boxtel

et al. 2014

Journal of Biological Chemistry

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“…The observation of high levels of alteration in antigenic variants of both major and minor surface structures/proteins during clonal replacement is more difficult to interpret but provides an indication that inclusion of major and minor antigens in a vaccine will prevent carriage of, and hence disease caused by, other strains carrying these antigens. This is particularly important as NadA is a component of a novel vaccine undergoing human trials (24), and others have proposed including both major and minor antigens in a meningococcal vaccine in order to provide a broader protective response (14).…”

Section: Discussionmentioning

confidence: 99%

Persistence, Replacement, and Rapid Clonal Expansion of Meningococcal Carriage Isolates in a 2008 University Student Cohort

et al. 2011

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A study of meningococcal carriage dynamics was performed with a cohort of 190 first-year students recruited from six residential halls at Nottingham University, United Kingdom. Pharyngeal swabs were obtained on four occasions between November 2008 and May 2009. Direct plating and culture on selective media were succeeded by identification and characterization of meningococci using PCR-based methodologies. Three serogroup Y clones and one serogroup 29E clone were highly prevalent in particular residential halls in November 2008, which is indicative of rapid clonal expansion since the start of the academic year. Persistent carriage of the same meningococcal strain for at least 5 to 6 months was observed in 45% of carriers, with infrequent evidence of antigenic variation in PorA. Sequential carriage of heterologous meningococcal strains occurred in 36% of carriers and involved strains with different capsules and antigenic variants of PorA and FetA in 83% of the cases. These clonal replacement strains also exhibited frequent differences in the presence and antigenic structures of two other surface proteins, NadA and HmbR. This study highlights the low level of antigenic variation associated with persistent carriage but, conversely, the importance of alterations in the repertoire of antigenic variants for sequential carriage of meningococcal strains. Rapid clonal expansion of potentially pathogenic strains in residential halls has implications for the implementation of public health interventions in university populations.

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“…10 Both NHBA and fHbp enhance the survival of the bacteria in human blood. 11,12 The OMV from the New Zealand outbreak strain, a component which independently has shown strain-specific vaccine effectiveness in infants beginning from six weeks of age, 3,6 contains the serosubtype PorA 1.4. To assess the possibility for broad protection across strains that may exhibit subtle differences in genotypic and phenotypic expression of surface proteins or future mutability, [7][8][9] investigational vaccine formulations incorporating only the recombinant antigens (rMenB) and formulations containing the recombinant antigens with OMV from the Norwegian (NW) outbreak strain (rMenB+OMVNW) or the New Zealand outbreak strain OMV (4CMenB) were developed.…”

Section: Introductionmentioning

confidence: 99%

The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans

Toneatto¹,

Ismaili²,

Ypma³

et al. 2011

Human Vaccines

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IntroductionNeisseria meningitidis serogroup B is a well-recognized cause of meningitis and septicemia for which no broadly protective vaccine exists. 1,2 Although vaccines against serogroups A, C, W-135 and Y are widely available, these vaccines are based on capsular polysaccharides, which in serogroup B are poorly immunogenic. 1The only vaccines that have been successfully used to protect against meningococcal serogroup B are those based on individual outer membrane vesicles derived from specific epidemic or outbreak strains.3-6 These vaccines have not shown cross-protection against heterologous strains in clinical studies. 1,2To provide broad protection and minimize the opportunity for escape mutations by single serogroup B strains, a multiple antigen approach was used to develop an investigational vaccine. Whole genome sequencing was used to identify novel surface proteins that were conserved across many strains and could be expected to induce bactericidal activity based on the results of studies in animal models. 7,8 The investigational vaccines developed against serogroup B contain three major recombinant Background: Neisseria meningitidis serogroup B is a well-recognized cause of bacterial meningitis and sepsis for which no broadly protective vaccine exists. Whole genome sequencing was used to identify three antigens: factor H binding protein (fHbp), Neisserial adhesin a (Nada) and Neisseria heparin binding antigen (NHBa) for an investigational vaccine candidate (rMenB). This was the first trial of an investigational multicomponent meningococcal serogroup B vaccine (4cMenB), containing rMenB and outer membrane vesicles (OMV) from the New Zealand epidemic strain in humans. Results: seventy adults enrolled and received study vaccine. all vaccines were generally well tolerated. Immune responses were observed to multiple serogroup B strains following all investigational vaccines, suggesting the potential for broad coverage against this serogroup. Immunogenicity was enhanced by the addition of OMV; the 4cMenB displayed the optimal profile for further investigation. Methods: In a phase I, observer blind, randomized trial, healthy adults (18-40 years of age) were randomized 2:2:1 to receive 3 doses of 4cMenB, rMenB with OMV from the Norwegian outbreak strain or rMenB alone. pre-and postvaccination sera were evaluated in a serum bactericidal assay using human complement (hsBa) against a panel of 15 serogroup B strains, with titers ≥4 considered protective. solicited injection site and systemic reactions were evaluated for 7 days following each vaccination and adverse events were reported throughout the study. conclusion: In this trial, 4cMenB displayed a favorable profile for further clinical development. 4cMenB demonstrated immunogenicity against multiple heterologous serogroup B strains. all vaccines were generally well tolerated in this study.

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Influence of serogroup B meningococcal vaccine antigens on growth and survival of the meningococcus in vitro and in ex vivo and in vivo models of infection

Cited by 33 publications

References 42 publications

Involvement of Neisseria meningitidis Lipoprotein GNA2091 in the Assembly of a Subset of Outer Membrane Proteins

Involvement of Neisseria meningitidis Lipoprotein GNA2091 in the Assembly of a Subset of Outer Membrane Proteins

Persistence, Replacement, and Rapid Clonal Expansion of Meningococcal Carriage Isolates in a 2008 University Student Cohort

The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans

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