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Article ; Online: Impact of Vaccines; Health, Economic and Social Perspectives

Charlene M. C. Rodrigues / Stanley A. Plotkin

Frontiers in Microbiology, Vol

2020 Volume 11

Abstract: In the 20th century, the development, licensing and implementation of vaccines as part of large, systematic immunization programs started to address health inequities that existed globally. However, at the time of writing, access to vaccines that prevent ...

Abstract	In the 20th century, the development, licensing and implementation of vaccines as part of large, systematic immunization programs started to address health inequities that existed globally. However, at the time of writing, access to vaccines that prevent life-threatening infectious diseases remains unequal to all infants, children and adults in the world. This is a problem that many individuals and agencies are working hard to address globally. As clinicians and biomedical scientists we often focus on the health benefits that vaccines provide, in the prevention of ill-health and death from infectious pathogens. Here we discuss the health, economic and social benefits of vaccines that have been identified and studied in recent years, impacting all regions and all age groups. After learning of the emergence of SARS-CoV-2 virus in December 2019, and its potential for global dissemination to cause COVID-19 disease was realized, there was an urgent need to develop vaccines at an unprecedented rate and scale. As we appreciate and quantify the health, economic and social benefits of vaccines and immunization programs to individuals and society, we should endeavor to communicate this to the public and policy makers, for the benefit of endemic, epidemic, and pandemic diseases.
Keywords	immunization ; vaccines ; infectious diseases ; infection ; children ; health economics ; Microbiology ; QR1-502 ; covid19
Subject code	360
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A world without bacterial meningitis

Charlene M.C. Rodrigues / Martin C.J. Maiden

F1000Research, Vol

how genomic epidemiology can inform vaccination strategy [version 1; referees: 2 approved]

2018 Volume 7

Abstract: Bacterial meningitis remains an important cause of global morbidity and mortality. Although effective vaccinations exist and are being increasingly used worldwide, bacterial diversity threatens their impact and the ultimate goal of eliminating the ... ...

Abstract	Bacterial meningitis remains an important cause of global morbidity and mortality. Although effective vaccinations exist and are being increasingly used worldwide, bacterial diversity threatens their impact and the ultimate goal of eliminating the disease. Through genomic epidemiology, we can appreciate bacterial population structure and its consequences for transmission dynamics, virulence, antimicrobial resistance, and development of new vaccines. Here, we review what we have learned through genomic epidemiological studies, following the rapid implementation of whole genome sequencing that can help to optimise preventative strategies for bacterial meningitis.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci

Mingliang Chen / Odile B. Harrison / Holly B. Bratcher / Zhiyan Bo / Keith A. Jolley / Charlene M.C. Rodrigues / James E. Bray / Qinglan Guo / Xi Zhang / Min Chen / Martin C.J. Maiden

Emerging Infectious Diseases, Vol 27, Iss 4, Pp 1110-

2021 Volume 1122

Abstract: Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. To determine the ...

Abstract	Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. To determine the relationship among globally distributed CC4821 meningococci, we analyzed whole-genome sequence data from 173 CC4821 meningococci isolated from 4 continents during 1972–2019. These meningococci clustered into 4 sublineages (1–4); sublineage 1 primarily comprised of IMD isolates (41/50, 82%). Most isolates from outside China (40/49, 81.6%) formed a distinct sublineage, the Europe–USA cluster, with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(CC4821), harboring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone ChinaCC4821-R1-C/B has expanded to other countries. The increasing distribution worldwide of serogroup B CC4821 raises the concern that CC4821 has the potential to cause a pandemic that would be challenging to control, despite indirect evidence that the Trumenba vaccine might afford some protection.
Keywords	Neisseria meningitidis ; meningitis/encephalitis ; ST4821 clonal complex ; bacteria ; genome ; phylogenetic analysis ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic Surveillance of 4CMenB Vaccine Antigenic Variants among Disease-Causing Neisseria meningitidis Isolates, United Kingdom, 2010–2016

Charlene M.C. Rodrigues / Jay Lucidarme / Ray Borrow / Andrew Smith / J. Claire Cameron / E. Richard Moxon / Martin C.J. Maiden

Emerging Infectious Diseases, Vol 24, Iss 4, Pp 673-

2018 Volume 682

Abstract: In September 2015, 4CMenB meningococcal vaccine was introduced into the United Kingdom infant immunization program without phase 3 trial information. Understanding the effect of this program requires enhanced surveillance of invasive meningococcal ... ...

Abstract	In September 2015, 4CMenB meningococcal vaccine was introduced into the United Kingdom infant immunization program without phase 3 trial information. Understanding the effect of this program requires enhanced surveillance of invasive meningococcal disease (IMD) Neisseria meningitidis isolates and comparison with prevaccination isolates. Bexsero Antigen Sequence Types (BASTs) were used to analyze whole-genome sequences of 3,073 prevaccine IMD N. meningitidis isolates obtained during 2010−2016. Isolates exhibited 803 BASTs among 31 clonal complexes. Frequencies of antigen peptide variants were factor H binding protein 1, 13.4%; Neisserial heparin-binding antigen 2, 13.8%; Neisseria adhesin A 8, 0.8%; and Porin A-VR2:P1.4,10.9%. In 2015−16, serogroup B isolates showed the highest proportion (35.7%) of exact matches to >1 Bexsero components. Serogroup W isolates showed the highest proportion (93.9%) of putatively cross-reactive variants of Bexsero antigens. Results highlighted the likely role of cross-reactive antigens. BAST surveillance of meningococcal whole-genome sequence data is rapid, scalable, and portable and enables international comparisons of isolates.
Keywords	Neisseria meningitidis ; bacteria ; genomic surveillance ; molecular epidemiology ; multilocus sequence typing ; MLST ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens [version 2; peer review

Charlene M. C. Rodrigues / Hannah Chan / Caroline Vipond / Keith Jolley / Odile B. Harrison / Jun Wheeler / Gail Whiting / Ian M. Feavers / Martin C. J. Maiden

Wellcome Open Research, Vol

2 approved]

2019 Volume 3

Abstract: Background: Protein-conjugate capsular polysaccharide vaccines can potentially control invasive meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups. Concerns raised by immunological similarity of the serogroup ... ...

Abstract	Background: Protein-conjugate capsular polysaccharide vaccines can potentially control invasive meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups. Concerns raised by immunological similarity of the serogroup B capsule to human neural cell carbohydrates, meant that ‘serogroup B substitute’ vaccines target more variable subcapsular protein antigens. A successful approach using outer membrane vesicles (OMVs) as major vaccine components had limited strain coverage. In 4CMenB (Bexsero®), recombinant proteins have been added to ameliorate this problem. Methods: Scalable, portable, genomic techniques were used to investigate the Bexsero® OMV protein diversity in meningococcal populations. Shotgun proteomics identified 461 proteins in the OMV, defining a complex proteome. Amino acid sequences for the 24 proteins most likely to be involved in cross-protective immune responses were catalogued within the PubMLST.org/neisseria database using a novel OMV peptide Typing (OMVT) scheme. Results: Among these proteins there was variation in the extent of diversity and association with meningococcal lineages, identified as clonal complexes (ccs), ranging from the most conserved peptides (FbpA, NEISp0578, and putative periplasmic protein, NEISp1063) to the most diverse (TbpA, NEISp1690). There were 1752 unique OMVTs identified amongst 2492/3506 isolates examined by whole-genome sequencing (WGS). These OMVTs were grouped into clusters (sharing ≥18 identical OMVT peptides), with 45.3% of isolates assigned to one of 27 OMVT clusters. OMVTs and OMVT clusters were strongly associated with cc, genogroup, and Bexsero® antigen variants, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with genogroup and Bexsero® Antigen Sequence Type. This highly structured population of IMD-associated meningococci is consistent with strain structure models invoking host immune and/or metabolic selection. Conclusions: The OMVT scheme facilitates ...
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular diagnostic assays for the detection of common bacterial meningitis pathogens

Kanny Diallo / Vitalis F. Feteh / Lilian Ibe / Martin Antonio / Dominique A. Caugant / Mignon du Plessis / Ala-Eddine Deghmane / Ian M. Feavers / Katya Fernandez / LeAnne M. Fox / Charlene M.C. Rodrigues / Olivier Ronveaux / Muhamed-Kheir Taha / Xin Wang / Angela B. Brueggemann / Martin C.J. Maiden / Odile B. Harrison

EBioMedicine, Vol 65, Iss , Pp 103274- (2021)

A narrative review

2021

Abstract: Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that ... ...

Abstract	Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use.
Keywords	Meningitis ; Bacteria ; Molecular diagnostics ; PCR ; RT-PCR ; LAMP assay ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Mingliang Chen / Charlene M. C. Rodrigues / Odile B. Harrison / Chi Zhang / Tian Tan / Jian Chen / Xi Zhang / Min Chen / Martin C. J. Maiden

Scientific Reports, Vol 8, Iss 1, Pp 1-

Invasive meningococcal disease in Shanghai, China from 1950 to 2016: implications for serogroup B vaccine implementation

2018 Volume 1

Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

Abstract	A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens [version 1; referees

Charlene M. C. Rodrigues / Hannah Chan / Caroline Vipond / Keith Jolley / Odile B. Harrison / Jun Wheeler / Gail Whiting / Ian M. Feavers / Martin C. J. Maiden

Wellcome Open Research, Vol

2 approved]

2018 Volume 3

Abstract	Background: Protein-conjugate capsular polysaccharide vaccines can potentially control invasive meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups. Concerns raised by immunological similarity of the serogroup B capsule, to human neural cell carbohydrates, has meant that ‘serogroup B substitute’ vaccines target more variable subcapsular protein antigens. A successful approach using outer membrane vesicles (OMVs) as major vaccine components had limited strain coverage. In 4CMenB (Bexsero®), recombinant proteins have been added to ameliorate this problem. Methods: Here, scalable, portable, genomic techniques were used to investigate the Bexsero® OMV protein diversity in meningococcal populations. Shotgun proteomics identified 461 proteins in the OMV, defining a complex proteome. Amino acid sequences for the 24 proteins most likely to be involved in cross-protective immune responses were catalogued within the PubMLST.org/neisseria database using a novel OMV peptide Typing (OMVT) scheme. Results: Among these proteins there was variation in the extent of diversity and association with meningococcal lineages, identified as clonal complexes (ccs), ranging from the most conserved peptides (FbpA, NEISp0578, and putative periplasmic protein, NEISp1063) to the most diverse (TbpA, NEISp1690). There were 1752 unique OMVTs identified amongst 2492/3506 isolates examined by whole-genome sequencing (WGS). These OMVTs were grouped into clusters (sharing ≥18 identical OMVT peptides), with 45.3% of isolates assigned to one of 27 OMVT clusters. OMVTs and OMVT clusters were strongly associated with cc, genogroup, and Bexsero® antigen variants, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with genogroup and Bexsero® Antigen Sequence Type. This highly structured population of IMD-associated meningococci is consistent with strain structure models invoking host immune selection. Conclusions: The OMVT scheme facilitates ...
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation

Brehony, Carina / Andrew Smith / Charlene M.C. Rodrigues / E. Richard Moxon / Martin C.J. Maiden / Ray Borrow / Robert Cunney

Vaccine. 2016 Sept. 07, v. 34, no. 39

2016

Abstract: Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup ... ...

Abstract	Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8–30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates.
Keywords	antigens ; cost effectiveness ; data collection ; databases ; genomic libraries ; genotype-phenotype correlation ; geographical variation ; immunity ; immunization ; infants ; meningitis ; models ; monitoring ; Neisseria meningitidis ; sequence analysis ; serotypes ; vaccines ; Great Britain ; Ireland
Language	English
Dates of publication	2016-0907
Size	p. 4690-4697.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2016.08.015
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: UKMenCar4

Holly B. Bratcher / Charlene M. C. Rodrigues / Adam Finn / Mandy Wootton / J. Claire Cameron / Andrew Smith / Paul Heath / Shamez Ladhani / Matthew D. Snape / Andrew J. Pollard / Richard Cunningham / Raymond Borrow / Caroline Trotter / Stephen J. Gray / Martin C. J. Maiden / Jenny M. MacLennan

Wellcome Open Research, Vol

A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence [version 2; peer review: 2 approved]

2019 Volume 4

Abstract: Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the ... ...

Abstract	Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through large, multi-centre carriage surveys of adolescents in 1999, 2000, and 2001, demonstrating carriage can be affected by immunisation with the capsular group C meningococcal conjugate vaccine, inducing population immunity against carriage. Fifteen years after these surveys were carried out, invasive meningococcal disease incidence had declined from a peak in 1999. The UKMenCar4 study was conducted in 2014/15 to investigate rates of carriage amongst the adolescent population during a period of low disease incidence. The protocols and methodology used to perform UKMenCar4, a large carriage survey, are described here.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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