A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

Martin, Natalie G; Snape, Matthew D.

doi:10.1586/14760584.2013.814862

Cited by 50 publications

(40 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a multicomponent protein-based vaccine against meningococcal group B (4CMenB) was licensed (23). To monitor vaccine-induced changes in meningococcal strains, extensive typing of invasive and carrier isolates will be necessary.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

et al. 2014

View full text Add to dashboard Cite

bNeisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These strains were chosen because each is mismatched for all but one of the vaccine antigens; therefore, each strain assesses the response to a single vaccine component (strain 44/76-SL for fHbp, strain 5/99 for NadA, strain NZ98/254 for the outer membrane vesicle and strain M10713 for NHBA). 10 Four additional strains (UKP1.7-2,4, GB101, GB355 and GB364), which reflected UK epidemiology and which had been used in the previous studies, were used to assess the vaccines' ability to induce a cross-reactive hSBA response to genetically diverse meningococcal serogroup B strains. Of note, earlier published studies referred to these strains as M00-242922 (UKP1.7-2,4), M01-240101 (GB101), M01-240355 (GB355) and M01-240364 (GB364).…”

Section: Immunogenicitymentioning

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

View full text Add to dashboard Cite

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...

show abstract

“…In addition, the safety profile of the combined vaccine was not different from those previously seen after the administration of separate monovalent vaccines (1,6,9). Although this work contributed to the concept of combining OMV vaccines to cover a broader range of epidemic strains, important steps toward improved epidemic coverage in different age groups has thereafter been taken by the development of a multicomponent serogroup B vaccine consisting of MeNZB OMV admixed with recombinant antigens (4CMenB) (19)(20)(21). Although such vaccines have been …”

mentioning

confidence: 93%

Cellular Immune Responses in Humans Induced by Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines Given Separately and in Combination

Oftung

Korsvold

Aase

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

MenBvac and MeNZB are safe and efficacious outer membrane vesicle (OMV) vaccines against serogroup B meningococcal disease. Antibody responses have previously been investigated in a clinical trial with these two OMV vaccines given separately (25 g/dose) or in combination (12.5 and 12.5 g/dose) in three doses administered at 6-week intervals. Here, we report the results from analyzing cellular immune responses against MenBvac and MeNZB OMVs in terms of antigen-specific CD4 ؉ T cell proliferation and secretion of cytokines. The proliferative CD4؉ T cell responses to the combined vaccine were of the same magnitude as the homologous responses observed for each individual vaccine. The results also showed cross-reactivity in the sense that both vaccine groups receiving separate vaccines responded to both homologous and heterologous OMV antigen when assayed for antigen-specific cellular proliferation. In addition, a multiplex bead array assay was used to analyze the presence of Th1 and Th2 cytokines in cell culture supernatants. The results showed that gamma interferon, interleukin-4 (IL-4), and IL-10 responses could be detected as a result of vaccination with both the MenBvac and the MeNZB vaccines given separately, as well as when given in combination. With respect to cross-reactivity, the cytokine results paralleled the observations made for proliferation. In conclusion, the results demonstrate that cross-reactive cellular immune responses involving both Th1 and Th2 cytokines can be induced to the same extent by different tailor-made OMV vaccines given either separately or in combination with half the dose of each vaccine. N eisseria meningitidis serogroup B vaccines based on outer membrane vesicles (OMVs) from defined serogroup B strains have been shown to be efficacious to control clonal outbreaks in several countries, including Norway, Cuba, and New Zealand (1-3). The PorA protein is the immunodominant antigen in OMV vaccines and elicits protective immune responses (4). PorA shows large sequence variation between strains, and a limitation of OMV vaccines is that they induce mainly strain-specific antibodies (5), but cross-protective antibodies against other B strains have been observed in small children and adults (3, 5). The OMV vaccine MenBvac was developed based on the B:15:P1.7,16 strain representative of the previous meningococcal epidemic in Norway. Based on several clinical trials, this vaccine has been shown to be safe, immunogenic, and to confer protection against meningococcal B disease (6-9). MenBvac has also recently been used to combat an outbreak of serogroup B disease in France demonstrating that OMV vaccines can be efficient against heterologous B strains provided that they are sufficiently immunologically close (10, 11).A similar meningococcal serogroup B OMV vaccine (MeNZB) based on a different strain (B:4:P1.7-2,4) was developed and introduced in 2004 to control the meningococcal epidemic in New Zealand (12)(13)(14) showing more than 70% effectiveness (3). However, in most geographical regions ...

show abstract

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

Cited by 50 publications

References 91 publications

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

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

Cellular Immune Responses in Humans Induced by Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines Given Separately and in Combination

Contact Info

Product

Resources

About