A ‘tailor made’ vaccine trialled as part of public health response to group B meningococcal epidemic in New Zealand

Holst, Johan; Aaberge, Ingeborg S.; Oster, Philipp; Lennon, Diana; Martin, Diana; O’Hallahan, Jane; Nord, K.; Nøkleby, Hanne; Næss, Lisbeth Meyer; Kristiansen, Paul A.; Skryten, A G; Bryn, Klaus; Aase, Audun; Rappuoli, Rino; Rosenqvist, E

doi:10.2807/esw.07.30.02262-en

Cited by 14 publications

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“…The OMVs were purified by fractionated centrifugation and adsorbed to aluminum hydroxide (9). MeNZB was prepared at NIPH by a similar technique from a B:4:P1.7-2,4 meningococcal strain (strain NZ98/254) (11). This strain was kindly provided by Diana Martin of the Institute of Environmental Science and Research, Porirua, New Zealand.…”

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confidence: 99%

Immunogenicity and Safety of a Combination of Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines

Sandbu

Feiring

Oster

et al. 2007

Clin Vaccine Immunol

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MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 g), MeNZB (25 g), or the MenBvac and MeNZB (doses of 12.5 g of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of >4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries.

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confidence: 99%

Immunogenicity and Safety of a Combination of Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines

Sandbu

Feiring

Oster

et al. 2007

Clin Vaccine Immunol

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“…This strain type accounted for 85.9% of 2,511 group B case isolates identified from 1991 through 2004 (1,8). To control the epidemic, a strain-specific outer membrane vesicle (OMV) vaccine, MeNZB, was developed by Chiron Vaccines, in association with the Norwegian Institute of Public Health (5,14,20). Age group clinical trials were conducted with school-age children enrolled between ages 8 and 12 years, toddlers between 16 and 24 months, older infants between 6 and 8 months, and young infants between 6 and 10 weeks.…”

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The VR2 Epitope on the PorA P1.7-2,4 Protein Is the Major Target for the Immune Response Elicited by the Strain-Specific Group B Meningococcal Vaccine MeNZB

Martin

Ruijne

McCallum

et al. 2006

Clin Vaccine Immunol

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A protracted epidemic of group B meningococcal disease in New Zealand led to the testing of a strain-specific tailor-made vaccine, MeNZB. Immunogenicity levels achieved during age group trials enabled New Zealand's regulatory authority to grant licensure to deliver MeNZB to all individuals under age 20. During the trials target strains for serum bactericidal antibody measurements included the vaccine target strain NZ98/254 and two comparator epidemic-type strains (NZ94/167 and NZ02/09). In this study, 12 other strains differing variously from the vaccine strain by their capsular group, PorB type, and PorA variable region specificities, or PorA expression, were used as target strains. The PorA specificity of the serum bactericidal antibody responses to the vaccine was determined for 40 vaccinees. Sets of 10 pre-and postvaccination sera were chosen randomly from the young infant, older infant, toddler, and school-age group trials. Antibody recognition of linearized PorA proteins was also determined using immunoblotting. Across all age groups vaccine-induced serum bactericidal antibodies specifically targeted the VR2 P1.4 epitope of the PorA P1.7-2,4 protein irrespective of the PorB type and/or capsular type of the target strain. Deletion of amino acids within the VR2 epitope or replacement of the epitope through genetic exchange allowed strains variously to resist antibody-directed complement-mediated lysis and negated PorA-specific antibody recognition in immunoblots. The demonstration that the immunodominant antibody response was specifically for the VR2 P1.4 epitope of the PorA protein supports the public health decision to use a strain-specific vaccine for the control of New Zealand's epidemic of meningococcal disease.

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“…In contrast to the abrupt onset and short duration of epidemics caused by serogroup A meningococcus in sub-Saharan Africa, the epidemics of serogroup B develop gradually over several years and may last substantially more than ten years. 7,8 Clonal outbreaks of serogroup B organisms have been responsible for epidemics in the Americas (Cuba, Brazil, Chile and the United States) and Europe (Iceland, Norway, Belgium and Spain). 9 New Zealand also experienced an outbreak of a single clone of meningococcal B disease starting in 1991.…”

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confidence: 99%

“…This vaccine was "tailor-made" for the epidemic in New Zealand, using an isolate representative of the epidemic as the production strain for vaccine manufacture. 8 After three years of a successful vaccine campaign, the vaccine efficacy was recently estimated to approximately 80%. 11 The epidemiology of endemic meningococcal disease in many developed countries is currently dominated by serogroup B disease.…”

Section: Introductionmentioning

confidence: 99%

Strategies for Development of Universal Vaccines Against Meningococcal Serogroup B Disease

Holst¹

2007

Human Vaccines

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A vaccine inducing protection against most of the circulating variants of serogroup B meningococcal strains is not yet available. A number of plausible options are currently under investigation. A conjugate vaccine based on a modified capsular polysaccharide might well work, but has safety concerns from molecular mimicry between group B sialic acid and human tissue. Recently, however, the group B capsule has been shown to contain de-N-acetyl sialic acid residues that do not cross-react with normal host tissues and can then be the target of bactericidal antibodies. Potentially, this polysaccharide structure could form the basis of a safe and protective group B vaccine. Outer membrane vesicles (OMVs) from Neisseria lactamica avoid the immunodominant and highly strain specific immune response against the PorA protein, and are reported to elicit crossreactive protection in mice against lethality from challenge with meningococcal group B bacteria. However, the serum antibody responses lack bactericidal activity, and the mechanisms of protection are unknown. A number of universal, cross-reactive antigens have been identified through "reverse vaccinology" and successfully tested as recombinant protein vaccines. Promising results have also been demonstrated using OMV vaccines prepared from strains engineered for upregulation of conserved, cross-reactive antigens. This approach takes advantage of experience gained with conventional wild-type OMV vaccines and the large number of new antigens identified through sequencing the genome of N. meningitidis. Initial studies show that the traditional use of detergents to decrease toxicity by extraction of lipopolysaccharides (LPS) should, if possible, be omitted in order to avoid extraction of important lipoproteins. In the absence of detergent extraction, clinical OMV formulations with acceptable toxicity may still be achieved by constructing vaccine production strains with genetically detoxified LPS. Thus, a MenB vaccine might be designed based on non-cross-reactive capsular antigens, OMV vaccines from genetically modified strains, recombinant proteins or a combination of these approaches. Given all of the recent data available and experience gained, the possibility for development of a universal vaccine for prevention of group B meningococcal disease looks promising. For evaluation of vaccine formulations relying on cross-reactive proteins, selection of strains for representation of the global epidemiological situation will be of outmost importance. Defining criteria for establishing and revising such strain collections is currently ongoing and will be a key element in developing and evaluating new protein based vaccines in the time to come.

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A ‘tailor made’ vaccine trialled as part of public health response to group B meningococcal epidemic in New Zealand

Abstract: New Zealand has experienced an epidemic of serogroup B meningococcal infection since 1991

Cited by 14 publications

References 0 publications

Immunogenicity and Safety of a Combination of Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines

Immunogenicity and Safety of a Combination of Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines

The VR2 Epitope on the PorA P1.7-2,4 Protein Is the Major Target for the Immune Response Elicited by the Strain-Specific Group B Meningococcal Vaccine MeNZB

Strategies for Development of Universal Vaccines Against Meningococcal Serogroup B Disease

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