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Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease
Örebro University, School of Health and Medical Sciences.
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2009 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 10, p. 1579-1584Article in journal (Refereed) Published
Abstract [en]

During the recent years, projects are in progress for designing broad-range non-capsular-based meningococcal vaccines, covering also serogroup B isolates. We have examined three genes encoding antigens (NadA, GNA1030 and GNA2091) included in a novel vaccine, i.e. the 5 Component Vaccine against Meningococcus B (5CVMB), in terms of gene prevalence and sequence variations. These data were combined with the results from a similar study, examining the two additional antigens included in the 5CVMB (fHbp and GNA2132).

nadA and fHbp v. 1 were present in 38% (n=36), respectively 71% (n=67) of the isolates, whereas gna2132, gna1030 and gna2091 were present in all the Neisseria meningitidis isolates tested (n=95). The level of amino acid conservation was relatively high in GNA1030 (93%), GNA2091 (92%), and within the main variants of NadA and fHbp. GNA2132 (54% of the amino acids conserved) appeared to be the most diversified antigen. Consequently, the theoretical coverage of the 5CVMB antigens and the feasibility to use these in a broad-range meningococcal vaccine is appealing.

Place, publisher, year, edition, pages
Amsterdam: Elsevier , 2009. Vol. 27, no 10, p. 1579-1584
Keywords [en]
Neisseria meningitidis; 5CVMB vaccine; Genome-derived neisserial antigen (GNA); sequencing; MLST
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-6635DOI: 10.1016/j.vaccine.2008.12.052OAI: oai:DiVA.org:oru-6635DiVA, id: diva2:214668
Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens
Open this publication in new window or tab >>Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neisseria meningitidis, also referred to as meningococcus, is a Gram-negative diplococcal bacterium best known as an important cause of meningitis and septicaemia worldwide. Meningococcal disease is a rare but life-threatening illness that may progress to death despite optimal medical care including appropriate antibiotic therapy. Case fatality remains high and survivors may suffer from significant sequelae because of impaired circulation and/or damages to the central nervous system. Prevention through vaccination remains a most effective approach to control disease. The main problem, however, is the absence of an effective vaccine against disease caused by a broad spectrum of group B isolates.

Understanding how the meningococcus can be both a common commensal and a devastating human pathogen is a major task for researchers in the area of meningococcal disease. In paper I, we investigated and described the characteristics of fatal meningococcal isolates and compared these with non-fatal invasive meningococcal isolates. The diversity was high within the isolates from both patient groups. Group Y, serotypes 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2 were more common in fatal cases as were being elderly and female.

The second major task in the area of meningococcal disease is to develop a group B vaccine. Six genes encoding antigens identified as promising vaccine candidates were examined in papers II & III. Based on our results, the prevalence of these genes and their sequence variation have the potential to constitute a meningococcal vaccine of broad range that also cover group B isolates in Sweden and other countries with a similar distribution of disease causing meningococci.

In paper IV, we investigated the levels of IgG antibodies in serum directed against fHbp and NadA, two of the antigens included in papers II & III. Overall, the immune response to fHbp seems to be higher than the immune response to NadA, with a clear rise of anti-fHbp in the young adult groups (20-29 years).

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. p. 92
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 31
Keywords
Neisseria meningitidis, meningococcal disease, risk factors, vaccine, genome-derived neisserial antigens (GNA), polymerase chain reaction (PCR), sequencing
National Category
Medical and Health Sciences
Research subject
Medicine; Biomedicine
Identifiers
urn:nbn:se:oru:diva-6638 (URN)978-91-7668-670-6 (ISBN)
Public defence
2009-06-05, Wilandersalen, Universitetssjukhuset Örebro, Örebro, 09:00 (Swedish)
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Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2017-10-18Bibliographically approved

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Jacobsson, SusanneUnemo, Magnus

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