Diversity of greek meningococcal serogroup B isolates and estimated coverage of the 4CMenB meningococcal vaccine

Tzanakaki, Georgina; Hong, Eva; Κεσανόπουλος, Κωνσταντίνος; Xirogianni, Athanasia; Bambini, Stefania; Orlandi, Luca; Comanducci, Maurizio; Muzzi, Alessandro; Taha, Muhamed‐Kheir

doi:10.1186/1471-2180-14-111

Cited by 43 publications

(32 citation statements)

References 33 publications

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“…tant isolates with moderately high FHbp expression in our study of 25 serogroup B clinical isolates, however, suggests a cautionary note about applying surrogate assays that only measure an isolate's FHbp expression and/or cross-reactivity with that of the vaccine antigen for predicting vaccine coverage without additional experimental data (7,(9)(10)(11)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 97%

Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity

Giuntini¹,

Pajón²,

Ram

et al. 2015

Infect Immun

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T wo meningococcal serogroup B vaccines contain factor H binding protein (FHbp) (1, 2). One of the vaccines, Bexsero (Novartis Vaccines), is licensed in Europe, Australia, and Canada for use in infants, older children, and adults. This vaccine also contains three other antigens capable of eliciting bactericidal antibodies (2) and is referred to as "4CMenB" (four component meningococcal B). The second vaccine, Trumenba (Pfizer), was licensed in the United States on 29 October 2014 for use with the age group from 10 to 25 years. This vaccine contains FHbp (see below).As of October 2014, there were 758 distinct amino acid sequence variants of FHbp, each assigned a unique "peptide" identifier (ID) as designated on a public database (http://pubmlst.org /neisseria/fHbp/). Based on amino acid sequence relatedness, FHbp sequence variants can be subdivided into two subfamilies, A and B (3, 4), or into three variant groups (5). There is general agreement that protection conferred by anti-FHbp antibody is subfamily (3) or variant group (5) specific. There is also general agreement that isolates with very low FHbp expression are resistant to anti-FHbp bactericidal activity and that isolates with relatively high expression are susceptible as long as there is an antigenic match between the FHbp sequence variant expressed by the isolate and that of the vaccine used to raise the antibody (6-8).The Pfizer FHbp vaccine contains two FHbp sequence variants, one from each subfamily. The Novartis 4CMenB vaccine contains only a subfamily B FHbp sequence variant. Antibodies elicited by the three other antigens in 4CMenB provide coverage against the majority of meningococci with subfamily A FHbp sequence variants. To date, defining threshold levels of FHbp expression and/or cross-reactivity that are sufficient for predicting susceptibility of an isolate to anti-FHbp bactericidal activity has largely been done empirically by correlating FHbp expression of isolates from different strain collections with susceptibility to bactericidal activity of serum pools from vaccinated infants or adolescents (9-11).In the present study, we identified four disease-causing serogroup B isolates with relatively high expression of FHbp that were resistant to complement-mediated bactericidal activity of sera from mice immunized with FHbp sequence variants that matched those of the isolates. As described below, two of the four isolates had evidence of human FH-dependent complement evasion independent of FHbp. We report the results of investigations of the basis for the anti-FHbp bactericidal resistance in these two isolates.

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Section: Discussionmentioning

confidence: 97%

Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity

Giuntini¹,

Pajón²,

Ram

et al. 2015

Infect Immun

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“…In Spain, most of the MenB strains seem to be covered by only one vaccine antigen: this might be due to the emergence of cc213 in Spain which is associated with low predicted MATS strain coverage (Abad et al, 2016). Nevertheless, a 4CMenB vaccine coverage was estimated to be 89.2 % (95 % confidence interval, 63.5-98.6 %) in Greece mainly due to the presence of NHBA-20 among cc162 MenB strains (Tzanakaki et al, 2014). Overall, as already mentioned (Brehony et al, 2015), a limited number of antigenic variants of each vaccine antigen were represented among MenB isolates, with an association with specific serogroups and ccs.…”

Section: Discussionmentioning

confidence: 99%

“…In the EU area, serogroup B is the predominant cause of IMD, followed by serogroup C, whereas serogroup Y is recently increasing (Bröker et al, 2015;Törös et al, 2014). The only successful meningococcal disease prevention tool is represented by conjugate vaccines, including both meningococcal serogroup C glycoconjugate vaccines and quadrivalent conjugate vaccines against serogroups A, C, Y and W. Moreover, a novel meningococcal multicomponent vaccine, four-component meningococcal serogroup B (4CMenB; Bexsero ® ), has been approved in Europe, Canada, Australia and USA.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of a collection of Neisseria meningitidis isolates from Croatia, June 2009 to January 2014

Bukovski¹,

Vacca

Anselmo³

et al. 2016

Journal of Medical Microbiology

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In the last decade, the incidence of invasive meningococcal disease (IMD) in Croatia remained stable at approximately 1 case per 100 000 inhabitants, affecting mainly children aged 5 years. We report the molecular characterization of meningococci causing IMD occurring from June 2009 to January 2014 in Croatia. Genomic DNA from 50 clinical isolates was analysed for serogroup, multilocus sequence typing and allele type of the two outer membrane protein genes, porA and the iron-regulated fetA. Furthermore, 22 of them were characterized by using whole-genome sequencing to define the meningococcal vaccine four-component meningococcal serogroup B (4CMenB) antigen genes factor H-binding protein (fHbp), Neisseria heparin-binding antigen (nhba) and Neisseria adhesin A (nadA) and the antimicrobial target resistance genes for penicillin (penicillin binding protein 2, penA), ciprofloxacin (DNA gyrase subunit A, gyrA) and rifampicin (b-subunit of RNA polymerase, rpoB). The Etest was used to phenotypically determine the antimicrobial susceptibility of isolated meningococci. The main serogroup/clonal complex combinations were MenB cc41/44, MenC/cc11, MenW/cc174 and MenY/cc23. PorA P1.7-2, FetA F5-5 and F1-5 were the most represented through the serogroups. Meningococci with decreased susceptibility to penicillin (38.9 %) and one strain resistant to ciprofloxacin were identified. Forty-two percent of MenB showed the presence of at least one of the 4CMenB vaccine antigens (fHbp, NHBA, NadA and PorA). Our findings highlight the genetic variability of meningococci causing IMD in Croatia, especially for the serogroup B. Molecular-based characterization of meningococci is crucial to enhance IMD surveillance and to better plan national immunization programmes. INTRODUCTIONInvasive meningococcal disease (IMD) is caused by Neisseria meningitidis, a strict human pathogen affecting mainly children 5 years of age, adolescents and young adults (Stephens, 2009). IMD is characterized by meningitis, sepsis and less commonly pneumonia, arthritis and pericarditis.According to the European Centre for Disease Prevention and Control (ECDC) data, the incidence of IMD reported in European Union (EU) and European Economic Area countries in 2012 was substantially low (ECDC, 2014), with an overall notification rate of 0.68 cases per 100 000 inhabitants. IMD case fatality ranged from 8 to 15 %, and approximately 10-20 % of survivors suffered from long-term sequelae including mental retardation, motor nerve deficit, hearing loss and loss of limbs (ECDC, 2014;Stephens, 2009). †These authors contributed equally to this work.

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“…The measurement of antigen expression and/or cross-reactivity by a meningococcal antigen typing system (MATS) has been used extensively to predict MenB-4C vaccine coverage (40)(41)(42)(43)(44). Further, the results have been reported to be a conservative predictor of coverage (45).…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

Rossi

Beernink

Giuntini

et al. 2015

Clin. Vaccine Immunol.

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M eningococcal serogroup B outbreaks involving a total of 14 cases occurred on two university campuses in the United States in 2013 and 2014 (1). The outbreak at university A, which is located in New Jersey, started in March 2013 with a total of 9 cases documented in the campus population or in close contacts of the students (2). The outbreak at university B, which is located in California, started in November 2013 with a cluster of four cases (1). These cases were later connected to a fifth case in a student enrolled at university B, which had occurred 7 months earlier. The strains from the two outbreaks were from different clonal complexes and therefore were not epidemiologically related.In response to these campus outbreaks, the U.S. Food and Drug Administration approved the immunization of the students with a serogroup B meningococcal vaccine (Bexsero; Novartis Vaccines and Diagnostics) (2), which at the time was licensed in Europe, Canada, and Australia. The vaccine contains four primary components, each capable of eliciting complement-mediated serum bactericidal activity (3, 4), and is referred to here as MenB-4C. The four antigens are factor H binding protein (FHbp), neisserial heparin binding antigen (NHba), neisserial adhesin A (NadA), and a porin protein (PorA) with variable region (VR) sequence type P1.7-2,4 contained in outer membrane vesicles (OMV) (3, 4). Since most of the anti-PorA bactericidal activity is directed to VR2, a match between the vaccine PorA and strain PorA is usually described as sharing the P1.4 VR2 antigen (5).The purpose of the present study was to investigate the expression of MenB-4C vaccine antigens in representative isolates from each of the outbreaks and the susceptibility of the isolates to serum bactericidal activity induced by MenB-4C vaccination. We also assessed the contribution of anti-FHbp antibodies in eliciting serum bactericidal activity. MATERIALS AND METHODSMeningococcal outbreak strains. We received 15 case isolates from the Meningitis Laboratory, Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention (CDC), Atlanta, GA. Of these, 10 isolates were from the university A outbreak, and 5 were from the university B outbreak. The CDC provided data on the date of isolation, source (blood or cerebrospinal fluid [CSF] sample), multilocus sequence type (MLST), PorB amino acid sequence type, and amino acid sequence variants of the FHbp, NadA, NHba, and PorA vaccine antigens. The isolates from university A were from sequence type 409 (ST-409), which is uncommon in the United States but part of the more common ST-41/44 clonal complex. The isolates from university B were all from ST-32, which is a common ST/clonal complex among invasive serogroup B case isolates from the west coast of the United States (6).Control strains. The strains used as controls are summarized in Table 1 and were previously described. Neisseria meningitidis strain NZ98/254 is a relatively low expresser of FHbp identification (ID) 14 (subfamily B) (7) and was use...

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Diversity of greek meningococcal serogroup B isolates and estimated coverage of the 4CMenB meningococcal vaccine

Cited by 43 publications

References 33 publications

Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity

Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity

Molecular characterization of a collection of Neisseria meningitidis isolates from Croatia, June 2009 to January 2014

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

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