Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme

Carr, Jeremy; MacLennan, Jenny; Plested, Emma; Bratcher, Holly B.; Harrison, Odile; Aley, Parvinder K.; Bray, James E.; Camara, Susana; Rodrigues, Charlene; Davis, Kimberly; Bartolf, Angela; Baxter, David; Cameron, J. Claire; Cunningham, Richard; Faust, Saul N.; Fidler, Katy; Gowda, Rohit; Heath, Paul T.; Hughes, Stephen; Khajuria, Sujata; Orr, David W.; Raman, Mala; Smith, Andrew; Turner, David P. J.; Whittaker, Elizabeth; Williams, Christopher J.; Zipitis, Christos S; Pollard, Andrew J.; Oliver, Jennifer; Morales-Aza, Begonia; Lekshmi, Aiswarya; Clark, S. A.; Borrow, Ray; Christensen, Hannah; Trotter, Caroline; Finn, Adam; Maiden, Martin C. J.; Snape, Matthew D; Jolley, Keith A.; Ford, Karen; Roberts, Hannah; Palmer, Karen; Suggitt, Debbie; Pemberton, Nicola; Ray, Samantha; Wootton, Mandy; Ladhani, Shamez; Owens, Daniel J.; Cathie, Katrina; Royal, Simon; Oldfield, Neil J.; Ure, Roisin; Richards, Jennifer; Ramsay, Rebecca; Hill, Samantha Thomson; Duale, Kaltun

doi:10.1016/j.cmi.2022.07.004

Cited by 36 publications

(25 citation statements)

References 27 publications

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“…Since baseline rates of menC and menW were low and carriage of menA was altogether absent in the 2018 study, this decline in vaccine-type carriage was mainly driven by a reduction in menY circulation (from 4.7% in 2018 to 0.7% in 2022; Fisher's Exact test, P<0.001). Our findings are in line with a meningococcal carriage study conducted among adolescents in the United Kingdom, where a decline in menACWY vaccine-type prevalence was observed three years after the vaccine was introduced to the national vaccination programme [15]. In the Netherlands, a significant decline in menW but not menY IMD incidence was noted after menACWY implementation in vaccine-noneligible age groups [16].…”

Section: Menacwy Vaccination Affected Genogroup Distribution In Carriagesupporting

confidence: 90%

Surveillance ofNeisseria meningitidisCarriage Four Years After menACWY Vaccine Implementation in the Netherlands Reveals Decline in Vaccine-type and Rise in Genogroup E Circulation

Miellet

Pluister

Sikking

et al. 2023

Preprint

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Carriage of Neisseria meningitidis is an accepted endpoint in monitoring meningococcal vaccine effects. We applied molecular methods to assess the impact of menACWY vaccine implementation on meningococcal carriage and genogroup-specific prevalence in young adults in Fall of 2022, four years after the introduction of the tetravalent vaccine in the Netherlands. The overall carriage rate of genogroupable meningococci was not significantly different compared to the pre-menACWY cohort investigated in 2018 (20.8% or 125 of 601 versus 17.4.% or 52 of 299 individuals, p=0.25). Of n=125 carriers of genogroupable meningococci n=122 (97.6%) were positive for either vaccine-types menC, menW, menY or non-vaccine types menB, menE, menX and menZ, Compared with a pre-vaccine-implementation baseline, there was 3.8-fold reduction (p<0.001) in vaccine-type carriage rates and 9.0-fold increase (p<0.0001) in non-vaccine type menE prevalence. These findings imply that menACWY vaccination reduced circulation of vaccine-type meningococci, but lead to serogroup replacement in carriage.

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Section: Menacwy Vaccination Affected Genogroup Distribution In Carriagesupporting

confidence: 90%

Surveillance ofNeisseria meningitidisCarriage Four Years After menACWY Vaccine Implementation in the Netherlands Reveals Decline in Vaccine-type and Rise in Genogroup E Circulation

Miellet

Pluister

Sikking

et al. 2023

Preprint

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“…There is much less diversity in the microbiome of the anterior nares and oropharynx of the elderly compared to middle-aged adults and, although Neisseria species have been identified in the elderly [ 42 ], there is a paucity of large-scale meningococcal carriage studies in this age group. Nasopharyngeal carriage of meningococci is a prerequisite for disease, and it has been shown that the MenACWY vaccine has reduced the overall carriage of Y:cc23 among adolescents [ 43 ]. Although older adults do not have access to meningococcal vaccines as many of these form part of childhood immunization schedules, carriage of different clonal complexes could be indirectly affected in this population through herd immunity.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Studies Identify an Association of Transferrin Binding Protein B Variation and Invasive Serogroup Y Meningococcal Disease in Older Adults

Maynard-Smith

Derrick

Borrow³

et al. 2022

The Journal of Infectious Diseases

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Background Neisseria meningitidis serogroup Y, especially ST-23 clonal complex (Y:cc23), represents a larger proportion of invasive meningococcal disease (IMD) in older adults compared to younger individuals. This study explored the meningococcal genetic variation underlying this association. Methods Maximum-likelihood phylogenies and the pangenome were analysed using whole genome sequence (WGS) data from 200 Y:cc23 isolates in the Neisseria PubMLST database. Genome-wide association studies (GWAS) were performed on WGS data from 250 Y:cc23 isolates from individuals with IMD aged ≥65 years versus < 65 years. Results Y:cc23 meningococcal variants did not cluster by age-group or disease phenotype in phylogenetic analyses. Pangenome comparisons found no differences in presence or absence of genes in IMD isolates from the different age groups. GWAS identified differences in nucleotide polymorphisms within the transferrin-binding protein B (tbpB) gene in isolates from individuals ≥65 years of age. TbpB structure modelling suggests these may impact binding of human transferrin. Conclusion These data suggest differential iron scavenging capacity amongst Y:cc23 meningococci isolated from older compared to younger patients. Iron acquisition is essential for many bacterial pathogens including the meningococcus. These polymorphisms may facilitate colonisation, thereby increasing the risk of disease in vulnerable older people with altered nasopharyngeal microbiomes and nutritional status.

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“…An observational study of meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme was used to estimate κ, the vaccine efficacy against carriage due to vaccine groups [5]. Carr et al [5] observed a 65% decrease in carriage prevalence from 2015 to 2018. Fitting our model to these study results produced a vaccine efficacy against carriage best estimate of 41% for ACWY strains [97.5% CI: 38-44] with 0% for all other strains.…”

Section: Model Structurementioning

confidence: 99%

“…However, the main focus of this modelling study was the short (2-5 years) impact. Routine vaccine uptake (2015 catch-up campaign) 13 years u 85% [5] 14-18 years u 70% [5] 18-25 years u 35% [5] Routine vaccine uptake (from 2016) 13 years u 85% [5] Vaccine efficacy against carriage κ 41% Estimated from fitting to [5] Duration of carriage 1/r 6 months [3] Vaccine efficacy against disease d 94% [6] Vaccine waning (time after vaccination) 1/w 10 years [3] κ sensitivity analysis is plotted in Supplementary Figure S3.…”

Section: Scenariosmentioning

confidence: 99%

Modelling the impact of COVID-19 and routine MenACWY vaccination on meningococcal carriage and disease in the UK

et al. 2023

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Country-wide social distancing and suspension of non-emergency medical care due to the COVID-19 pandemic will undoubtedly have affected public health in multiple ways. While nonpharmaceutical interventions are expected to reduce the transmission of several infectious diseases, severe disruptions to healthcare systems have hampered diagnosis, treatment, and routine vaccination. We examined the effect of this disruption on meningococcal disease and vaccination in the UK. By adapting an existing mathematical model for meningococcal carriage, we addressed the following questions: What is the predicted impact of the existing MenACWY adolescent vaccination programme? What effect might social distancing and reduced vaccine uptake both have on future epidemiology? Will catch-up vaccination campaigns be necessary? Our model indicated that the MenACWY vaccine programme was generating substantial indirect protection and suppressing transmission by 2020. COVID-19 social distancing is expected to have accelerated this decline, causing significant long-lasting reductions in both carriage prevalence of meningococcal A/C/W/Y strains and incidence of invasive meningococcal disease. In all scenarios modelled, pandemic social mixing effects outweighed potential reductions in vaccine uptake, causing an overall decline in carriage prevalence from 2020 for at least 5 years. Model outputs show strong consistency with recently published case data for England.

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Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme

Cited by 36 publications

References 27 publications

Surveillance ofNeisseria meningitidisCarriage Four Years After menACWY Vaccine Implementation in the Netherlands Reveals Decline in Vaccine-type and Rise in Genogroup E Circulation

Surveillance ofNeisseria meningitidisCarriage Four Years After menACWY Vaccine Implementation in the Netherlands Reveals Decline in Vaccine-type and Rise in Genogroup E Circulation

Genome-Wide Association Studies Identify an Association of Transferrin Binding Protein B Variation and Invasive Serogroup Y Meningococcal Disease in Older Adults

Modelling the impact of COVID-19 and routine MenACWY vaccination on meningococcal carriage and disease in the UK

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