Influence of Two Vaccination Campaigns on Genetic Diversity of Invasive Neisseria meningitidis Isolates in Northern Spain (1997–2008)

BACKGROUND: Neisseria meningitidis diversifies rapidly, due to its high recombination rates. The aim of this study was to analyze the possible impact of two vaccination campaigns (a once-off A/C polysaccharide vaccination campaign in people aged 18 months to 20 years old in 1997, and a meningococcal C conjugate vaccination campaign in children aged < or = 6 years old from 2000 to 2008) on diversification of the population of invasive isolates obtained between 1997 and 2008. All of the 461 available isolates were included (2, 319, 123, 11 and 6 belonging to serogroups A, B, C, Y and W-135, respectively). METHODOLOGY/PRINCIPAL FINDINGS: The isolates were analyzed for diversity using multilocus sequence typing, eBURST and the S.T.A.R.T.2 program. One hundred and seven sequence types (ST) and 20 clonal complexes were obtained. Five different STs (ST11, ST8, ST33, ST1163 and ST3496) included 56.4% of the isolates. With the exception of ST11, all other STs were associated with a specific serogroup. Epidemic circulation of serogroup C ST8 isolates was detected in 1997-1998, as well as epidemic circulation of ST11 isolates (serogroups B and C) in 2002-2004. The epidemic behavior of serogroup B ST11 (ST11_B:2a:P1.5) was similar, although with lesser intensity, to that of ST11 of serogroup C. Although clonality increased during epidemic years, the overall diversity of the meningococcal population did not increase throughout the 12 years of the study. CONCLUSION: The overall diversity of the meningococcal population, measured by the frequency of STs and clonal complexes, numbers of alleles, polymorphic sites, and index of association, remained relatively constant throughout the study period, contradicting previous findings by other researchers

Progressive Decrease in the Potential Usefulness of Meningococcal Serogroup B Vaccine (4CMenB, Bexsero (R)) in Gipuzkoa, Northern Spain

The effectiveness of a vaccine is determined not only by the immunogenicity of its components, but especially by how widely it covers the disease-causing strains circulating in a given region. Because vaccine coverage varies over time, this study aimed to detect possible changes that could affect vaccine protection during a specific period in a southern European region. The 4CMenB vaccine is licensed for use in Europe, Canada, and Australia and is mainly directed against Neisseria meningitidis serogroup B. This vaccine contains four main immunogenic components: three recombinant proteins, FHbp, Nhba and NadA, and an outer membrane vesicle [PorA P1.4]. The allelic distribution of FHbp, Nhba, NadA, and PorA antigens in 82 invasive isolates (B and non-B serogroups) isolated from January 2008 to December 2013 were analyzed. 4CMenB was likely protective against 61.8% and 50% of serogroup B and non-B meningococci, respectively, in the entire period, but between 2012 and 2013, the predicted protection fell below 45% (42.1% for serogroup B isolates). The observed decreasing trend in the predicted protection during the 6 years of the study (X-2 for trend = 4.68, p=0.03) coincided with a progressive decrease of several clonal complexes (e. g., cc11, cc32 and cc41/44), which had one or more antigens against which the vaccine would offer protection.This work was supported by a grant from the Education Department of the Basque Country Government to the UPV/EHU (IT656-13). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Genes that produce the antigens included in the 4CMenB vaccine detected among invasive <i>Neisseria meningitidis</i> isolates in Gipuzkoa, northern Spain (2008–2013).

<p>Genes that produce the antigens included in the 4CMenB vaccine detected among invasive <i>Neisseria meningitidis</i> isolates in Gipuzkoa, northern Spain (2008–2013).</p

Number and percentage of invasive isolates with genes encoding proteins targeted by the Bexsero vaccine according to the isolated clonal complexes (CC). Gipuzkoa, (Basque Country, northern Spain).

a<p>cc103 (n = 3); cc35 (<i>N</i> = 2); cc162 (<i>N</i> = 2); cc167 (<i>N</i> = 2); cc174 (<i>N</i> = 2); cc750 (<i>N</i> = 2); cc22 (<i>N</i> = 1); cc1117 (<i>N</i> = 1); singletons (<i>N</i> = 6).</p><p>Number and percentage of invasive isolates with genes encoding proteins targeted by the Bexsero vaccine according to the isolated clonal complexes (CC). Gipuzkoa, (Basque Country, northern Spain).</p

Diversity of the meningococcal population in the Basque Country, north of Spain, 1997–2008.

<p>The ratio between the number of isolates and four parameters (number of sequence types [ST], clonal complexes, alleles and polymorphic sites) is shown among 461 invasive meningococci.</p

Distribution by clonal complex, sequence type and PorA type of 319 serogroup B and 123 serogroup C invasive meningococci from the Basque Country, north of Spain (1997–2008).

<p><b>Bold</b><b>type</b> indicates sequence types represented by 10 or more isolates.</p

Annual distribution of serogroup ET15 variant of the ST11/ET37 complex.

<p>Annual distribution of serogroup B (n = 43) and C isolates (n = 63) belonging to the ET15 variant of the ET37 complex showing multilocus sequence type 11.</p

Serogroup, sequence type and clonal complex yearly frequency among 461 available invasive meningococci from the Basque Country, north of Spain (1997–2008).

1<p>Serogroups A (n = 2), Y (n = 11) and W-135 (n = 6) are not represented in the table.</p>2<p>New STs described in this article.</p>3<p>Ratio: the higher the value, the lower the diversity (greater clonality)</p>4<p><i>I_A</i>: indicates the frequency of recombination events. <i>I_A</i> = 0 indicates frequent recombination events and <i>I_A</i>>0 indicates increasing clonality due to a lack of recombination events.</p