Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage

Frosi, Giacomo; Biolchi, Alessia; Sapio, Morena Lo; Rigat, Fabio; Gilchrist, Stefanie; Lucidarme, Jay; Findlow, Jamie; Borrow, Ray; Pizza, Mariagrazia; Giuliani, Marzia M.; Medini, Duccio

doi:10.1016/j.vaccine.2013.08.006

Cited by 128 publications

(102 citation statements)

References 22 publications

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“…Data from studies using the Meningococcal Antigen Typing System, which aims to predict overall strain coverage, suggest that up to 88% of UK strains 15 and 66% of Canadian strains 16 will be covered by the 4CMenB vaccine; however, the key test will be how the vaccine performs when administered routinely to whole populations. The Saguenay-Lac-Saint-Jean region of Quebec, which has relatively high rates of serogroup B meningococcal disease, recently ran a vaccine campaign using the 4CMenB vaccine; 17 however, the Public Health Agency of Canada currently recommends vaccination only for those in defined high-risk groups.…”

Section: Resultsmentioning

confidence: 99%

Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months

McQuaid

Snape

John

et al. 2015

CMAJ

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Interpretation: Waning of immunity by 5 years of age occurred after receipt of the 4CMenB vaccine in infancy, even with an additional booster at 40 months. The 4CMenB vaccine is immunogenic and was fairly well tol erated by 5-year-old children, although injection-site pain was noteworthy. Trial registration: Clinical Trials.gov, no. NCT01027351 Abstract Research E216CMAJ, April 21, 2015, 187 (7) We present here the results of a follow-on study investigating the persistence of antibodies 18-20 months after the last dose in 5-year-old children previously immunized under a variety of schedules with 4CMenB vaccine or another investigational vaccine (recombinant protein serogroup B meningococcal [rMenB] vaccine), which lacks the outer membrane vesicle component of the 4CMenB vaccine. Since the original infant study, 7 4CMenB vaccine has emerged as the preferred vaccine, because addition of the outer membrane vesicle component improves the breadth of strain coverage; 8 however, the extension study continued follow-up for all of the original children, and all results are therefore presented here. MethodsThis phase 2, open-label, single-centre extension study ran from January 2010 to August 2012 and was approved by the Oxfordshire Research Ethics Committee B (reference 09/H0605/89).The primary immunogenicity objective of the extension study was to assess persistence of antibodies at 40 months of age, as reported previously. 9 Here, we present the secondary outcomes of antibody persistence at 60 months of age and the immunogenicity, safety and tolerability of a 2-dose catch-up regimen of 4CMenB vaccine administered at 60 and 62 months. ParticipantsIn the original infant study, 7 147 infants from the UK were recruited and randomly assigned, on a 2:2:1:1 ratio, to receive 4CMenB or rMenB vaccine at 2, 4, 6 and 12 months or to receive one of these vaccines at 12 months alone.Of these 147 infants, 70 participated in the 40-month extension study, 9 in which those who originally received 4 doses received 1 additional dose (at 40 mo) and those who originally received 1 dose received 2 additional doses (at 40 and 42 mo) of the vaccine originally received. These groups are referred to here as follows: 4CMenB 2, 4,6,12,40; rMenB 2,4,6,12,40; 4CMenB 12,40,42; and rMenB 12,40,42. A fifth group (referred to as 4CMenB 40,42) received 2 doses of 4CMenB vaccine only at 40 and 42 months. All of these children were invited to participate again at about 60 months of age, and an additional 50 healthy, vaccine-naive controls (referred to as 4CMenB 60,62) were recruited by mail. The study therefore included a total of 6 groups (see Figure 1).Exclusion criteria were as follows: any previous meningococcal vaccination or history of meningococcal disease, severe allergy to any component of the vaccine, and any serious chronic or progressive disease or suspected immune system impairment. Administration of other vaccines was not permitted within 30 days before or after meningococcal vaccination, with the exception of the influenza vaccine, which c...

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Section: Resultsmentioning

confidence: 99%

Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months

McQuaid

Snape

John

et al. 2015

CMAJ

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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%

“…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)(10)(11).…”

mentioning

confidence: 99%

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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“…Attempts have been made to evaluate the likely breadth of coverage across a larger range of strains without directly testing them by hSBA, most notably using the Meningococcal Antigen Typing System, which estimates coverage of 66% of disease-causing strains in Canada, 73% in England and Wales and 78% Europe-wide [6,7]. However, this has recently been shown to possibly underestimate coverage, which may be as high as 88% when assessed using representative MenB isolates in England and Wales [8]. Crucially, the above estimates are based on pooled serum taken from infants 1 month after KEYWORDS: 4CMenB .…”

Section: Predicting Vaccine Effectivenessmentioning

confidence: 99%

Will booster doses be required for serogroup B meningococcal vaccine?

McQuaid

Snape

2014

Expert Review of Vaccines

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Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage

Abstract: MATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents.

Cited by 128 publications

References 22 publications

Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months

Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months

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

Will booster doses be required for serogroup B meningococcal vaccine?

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