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Novel meningococcal 4CMenB vaccine antigens: prevalence and polymorphisms of the encoding genes in Neisseria gonorrhoeae
WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
Novartis V&D, Siena, Italy.
Novartis V&D, Siena, Italy.
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2012 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 9, p. 750-760Article in journal (Refereed) Published
Abstract [en]

The first cross-protective Neisseria meningitidis vaccine (focus on serogroup B), the protein-based 4 component meningococcus serogroup B (4CMenB), includes the New Zealand outer membrane vesicle and three main genome-derived neisserial antigens (GNAs). These GNAs are fHbp (fused to GNA2091), NHBA (fused to GNA1030) and NadA. In this study, the prevalence and polymorphisms of the nucleotide and amino acid sequences of the 4CMenB antigens in a temporally and geographically diverse collection of N. gonorrhoeae isolates (n similar to=similar to 111) were investigated. All the examined GNA genes, except the nadA gene, were present in all gonococcal isolates. However, 25 isolates contained premature stop codons in the fHbp gene and/or the nhba gene, resulting in truncated proteins. Compared with the 4CMenB antigen sequences in reference strain MC58, the gonococcal strains displayed 67.095.4% and 60.994.9% identity in nucleotide sequence and amino acid sequence, respectively, in the equivalent GNA antigens. The absence of NadA, lack of universal expression of fHbp and NHBA and the uncertainty regarding the surface exposure of fHbp as well as the function of NHBA in N. gonorrhoeae will likely limit the use of the identical 4CMenB antigens in a gonococcal vaccine. However, possible cross-immunity of 4CMenB with gonococci and expression and function of the equivalent gonococcal GNAs, as well as of more appropriate GNAs for a gonococcal vaccine, need to be further examined.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012. Vol. 120, no 9, p. 750-760
Keywords [en]
Neisseria gonorrhoeae, 4CMenB vaccine, genome-derived neisserial antigen (GNA)
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Pharmacology and Toxicology Immunology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-58673DOI: 10.1111/j.1600-0463.2012.02903.xISI: 000307444600009PubMedID: 22882265Scopus ID: 2-s2.0-84865291540OAI: oai:DiVA.org:oru-58673DiVA, id: diva2:1121628
Note

Funding Agencies:

Örebro County Council Research Committee  

Foundation for Medical Research at Örebro University Hospital, Sweden  

Novartis VD, Siena, Italy 

Available from: 2017-07-12 Created: 2017-07-12 Last updated: 2022-06-16Bibliographically approved
In thesis
1. Implementation of strategies for management and prevention of sexually transmitted infections with focus on Neisseria gonorrhoeae and Chlamydia trachomatis
Open this publication in new window or tab >>Implementation of strategies for management and prevention of sexually transmitted infections with focus on Neisseria gonorrhoeae and Chlamydia trachomatis
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sexually transmitted infections (STIs) are a public health issue of great importance worldwide, with effects on fertility and reproduction. Chlamydia trachomatis and Neisseria gonorrhoeae, causative agents of chlamydia and gonorrhoea, respectively, are the most common bacterial STIs with an estimated 127 million new global cases of chlamydia and 87 million new gonorrhoea cases. The continued emergence of antimicrobial resistance (AMR) in N. gonorrhoeae may in the future lead to an untreatable infection. Prevention of these infections and controlling the development of AMR rely on several strategies developed by the World Health Organization (WHO). This thesis aimed to implement several of these strategies, including supporting vaccine development for C. trachomatis and N. gonorrhoeae, evaluating molecular methods for detecting N. gonorrhoeae, predicting AMR and supporting surveillance of the spread and prevalence of AMR in N. gonorrhoeae. The present studies on a C. trachomatis recombinant vaccine antigen and the investigation of similarities of N. gonorrhoeae antigen amino acid sequences to the antigens included in the meningococcal vaccine 4CMenB contributed to the field of vaccine development for STIs. The assay SpeeDx ResistancePlus® GC performed well in detecting N. gonorrhoeae and predicting ciprofloxacin resistance and could be used in AMR surveillance and individualised treatment. In 2016, the first national genomic surveillance of all N. gonorrhoeae isolates in Sweden was performed. This national surveillance study included whole-genome sequencing combined with phenotypic AMR and epidemiological data, which provides valuable information on circulating strains, epidemiology and phylogeny. Greater knowledge of gonorrhoea and gonococcal AMR epidemiology could inform decisions on guidelines and prevention. It is essential to continue to implement WHO strategies at the national and global levels to prevent and control chlamydia and gonorrhoea infections.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2022. p. 104
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 267
Keywords
Neisseria gonorrhoeae, epidemiology, whole-genome sequencing, antimicrobial resistance (AMR), Chlamydia trachomatis, vaccine, strategies, management and prevention
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-98526 (URN)9789175294407 (ISBN)
Public defence
2022-06-17, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
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Available from: 2022-04-11 Created: 2022-04-11 Last updated: 2022-06-16Bibliographically approved

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Hadad, RonzaJacobsson, SusanneFredlund, HansUnemo, Magnus

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Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS)
Microbiology in the medical areaMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Pharmacology and ToxicologyImmunology in the medical area

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