Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr;24(4):673-682.
doi: 10.3201/eid2404.171480.

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

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

Charlene M C Rodrigues et al. Emerg Infect Dis. 2018 Apr.

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: 4CMenB; Bexsero; IMD; MLST; Neisseria meningitidis; United Kingdom; bacteria; epidemiologic year; genomic surveillance; invasive meningococcal disease; meningitis/encephalitis; meningococcal vaccines; meningococci; molecular epidemiology; multilocus sequence typing; vaccine antigenic variants; vaccines; whole-genome sequencing.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Clonal complex and serogroup distribution of invasive meningococcal disease isolates, United Kingdom, 2010–2016. A) Proportional contribution of each cc of disease-causing culture-confirmed meningococcal isolates by epidemiologic year. Other cc indicates ccs that were found in <20 isolates during the 6-year study period. B) Distribution of isolate serogroups by epidemiologic year. Serogroups shown had >10 isolates during the 6-year study period. Serogroups with <10 isolates (A, E, X, and Z) are shown in Table 1. CC, clonal complex; NG, nongroupable, W/Y, serogroups combined because of inconclusive serogrouping results.
Figure 2
Figure 2
Distribution of 4CMenB vaccine antigenic variants among invasive meningococcal disease isolates, United Kingdom, 2010–2016. A) Proportion of isolates with fHbp variants 1, 2, and 3 by epidemiologic year. Peptide 1 is found in the Bexsero 4CMenB vaccine (GlaxoSmithKline, Bentford, UK), and cross-reactive variants included in this analysis are all variant 1 peptides. B) Proportion of isolates with the 7 most prevalent NHBA peptides by epidemiologic year; all other peptide variants are in “other.” Peptide 2 is contained in Bexsero. C) Proportion of isolates with NadA variants 1, 2/3, and 4/5 by epidemiologic year; there were no isolates with NadA variant 6. Peptide 8 (variant 2/3) is contained in Bexsero. Values above columns indicate number of unique peptides. D) Frequency distribution of PorA-VR1 (horizontal axis) and PorA-VR2 (vertical axis) variants. Variants shown were those that had >20 isolates in the collection from the United Kingdom during 2010–2016. Bexsero contains the MeNZB OMV vaccine components, including variants PorA P1.7–2,4. Color scales show the frequency of isolates from highest (green) to lowest (red). fHbp, factor H binding protein; NadA, Neisseria adhesin A; NHBA, Neisserial heparin-binding antigen; OMV, outer membrane vesicles; PorA, porin A.
Figure 3
Figure 3
Nonoverlapping association of BAST and cc among invasive meningococcal disease isolates, United Kingdom, 2010–2016. Frequency distribution of BAST by CC for the 7 most frequently found ccs that represent 82.4% (2,533/3,073) of culture-confirmed invasive meningococcal disease isolates. BAST-220, -223, -4, and -19 contain an exact match with BAST-1. BAST-2, -8, -219, -222, -232, -226, -231, -229, and -236 contain a potentially cross-reactive match with BAST-1. BAST, Bexsero Antigen Sequence Type; CC, clonal complex.
Figure 4
Figure 4
Changes in BAST prevalence before and after Bexsero implementation among invasive meningococcal disease isolates, United Kingdom, 2010–2016. Frequency of BASTs is shown for the period before implementation of Bexsero vaccine, July 2010–August 2015 (dark blue), and after implementation, September 2015–June 2016 (light blue). The most frequently occurring BASTs preimplementation were 2,¶ 221, 219,¶ 220,# 222,¶ 267, 225, 223,# 1576, and 349. The most frequent BASTs postimplementation were 2,¶ 221, 219,¶ 225, 220,# 232,¶ 8,¶ 1576, 228, and 349. *p<0.00001; †p<0.01; ‡p<0.05; §p<0001; ¶BAST contains a potentially cross-reactive match to BAST-1; #BAST contains an exact match to BAST-1. BASTs with significant changes preimplementation and postimplementation were BAST-2 (fHbp 22, NHBA 29, NadA 6, PorA-VR1:5, and PorA-VR2:2), p<0.00001; BAST-221 (25; 7; 0; 5–1; 10–1), p = 0.006; BAST-220 (4; 2; 0; 7–2; 4), p = 0.02; BAST-232 (4; 2; 0; 12–1; 16), p = 0.01; and BAST-8 (22; 29; 121; 5; 2), p = 0.0005. BAST, Bexsero Antigen Sequence Type.

Similar articles

Cited by

References

    1. MacLennan J, Kafatos G, Neal K, Andrews N, Cameron JC, Roberts R, et al.; United Kingdom Meningococcal Carriage Group. Social behavior and meningococcal carriage in British teenagers. Emerg Infect Dis. 2006;12:950–7. 10.3201/eid1206.051297 - DOI - PMC - PubMed
    1. Christensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10:853–61. 10.1016/S1473-3099(10)70251-6 - DOI - PubMed
    1. Ladhani SN, Flood JS, Ramsay ME, Campbell H, Gray SJ, Kaczmarski EB, et al. Invasive meningococcal disease in England and Wales: implications for the introduction of new vaccines. Vaccine. 2012;30:3710–6. 10.1016/j.vaccine.2012.03.011 - DOI - PubMed
    1. Viner RM, Booy R, Johnson H, Edmunds WJ, Hudson L, Bedford H, et al. Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study. Lancet Neurol. 2012;11:774–83. 10.1016/S1474-4422(12)70180-1 - DOI - PubMed
    1. Salisbury D, Ramsay MK. Immunisation against infectious disease. London: The Stationery Office; 2006.

Publication types

MeSH terms

LinkOut - more resources