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Philipp Oster - One of the best experts on this subject based on the ideXlab platform.
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immunogenicity and safety of a combination of two serogroup b meningococcal outer Membrane Vesicle vaccines
Clinical and Vaccine Immunology, 2007Co-Authors: Synne Sandbu, Berit Feiring, Lisbeth Meyer Naess, Philipp Oster, Oddveig S Helland, Ingeborg S Aaberge, Audun Aase, Hilde Bakke, Annecathrine Kristoffersen, Kjersti M RydlandAbstract: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 μg), MeNZB (25 μg), or the MenBvac and MeNZB (doses of 12.5 μg 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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functional and specific antibody responses in adult volunteers in new zealand who were given one of two different meningococcal serogroup b outer Membrane Vesicle vaccines
Clinical and Vaccine Immunology, 2007Co-Authors: Elisabeth Wedege, Philipp Oster, Karin Bolstad, Einar Rosenqvist, Audun Aase, Tove Karin Herstad, Lisa Mccallum, Diana R MartinAbstract:This study presents detailed analyses of total and specific serum antibody levels among 26 and 24 adult volunteers before vaccination and after the third dose of the meningococcal serogroup B outer Membrane Vesicle (OMV) vaccines MeNZB and MenBvac, respectively, in a clinical trial in New Zealand (V. Thornton, D. Lennon, K. Rasanathan, J. O’Hallahan, P. Oster, J. Stewart, S. Tilman, I. Aaberge, B. Feiring, H. Nokleby, E. Rosenqvist, K. White, S. Reid, K. Mulholland, M. J. Wakefield, and D. Martin, Vaccine 24:1395‐1400, 2006). With the homologous vaccine strains as targets, both vaccines induced significant increases in serum bactericidal and opsonophagocytic activities and in the levels of immunoglobulin G (IgG) to OMV antigens in an enzyme-linked immunosorbent assay (ELISA) and to live meningococci by flow cytometry. They also induced high levels of activity against the heterologous strains, particularly in terms of opsonophagocytic activity and IgG binding to live bacteria. The antibody levels with the homologous and heterologous strains in the four assays showed high and significant positive correlations. Specific IgG binding to 10 major OMV antigens in each vaccine was measured by scanning of immunoblots; ELISAs for two antigens, lipopolysaccharide and Neisseria surface protein A (NspA), were also performed. Both vaccines elicited significant increases in IgG binding to all homologous and heterologous OMV antigens except NspA. The total IgG band intensity on the blots correlated significantly with the IgG levels determined by the OMV ELISA and flow cytometry. In conclusion, the results of the various immunological assays showed that both OMV vaccines gave rise to high levels of specific and cross-reacting antibodies. Since 1991, an epidemic of meningococcal disease in New Zealand has caused over 200 deaths and nearly 6,000 cases of disease in a population of 4 million people (www.moh.govt.nz). Most of the cases are caused by serogroup B strains, and from 1991 through 2004, 86% of these expressed the P1.7-2,4 (P1.7b,4) PorA and belonged to the sequence type 41/44 complex (lineage III) (13, 15). The majority of these strains also expressed the serotype 4 PorB protein (14). In contrast to the other capsular meningococcal polysaccharides, group B polysaccharide is poorly immunogenic in humans (65); and vaccines based on subcapsular antigens, such as outer Membrane proteins or outer Membrane Vesicles (OMVs) from various group B strains, have been developed and used in clinical trials (6, 9, 12, 18, 48). The experience of the Norwegian Institute of Public Health (NIPH) with the development and production of the OMV vaccine (MenBvac) for the protection trial in Norway (6, 19) led to a partnership with Chiron Vaccines (now Novartis Vaccines & Diagnostics) and the New Zealand Ministry of Health, in which NIPH developed and produced a tailor-made OMV vaccine (MeNZB) from a representative strain of the New Zealand epidemic (NZ98/254)
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persisting immune responses indicating long term protection after booster dose with meningococcal group b outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2006Co-Authors: Berit Feiring, Philipp Oster, Jan Fuglesang, Lisbeth M Naess, Oddveig S Helland, Sandrine Tilman, Einar Rosenqvist, Marianne Riise A Bergsaker, Hanne Nokleby, Ingeborg S AabergeAbstract:MenBvac is an outer Membrane Vesicle vaccine against systemic meningococcal disease caused by serogroup B Neisseria meningitidis. In this placebo-controlled double-blind study including 374 healthy adolescents, the safety and immunogenicity of a schedule of three primary doses 6 weeks apart followed by a fourth dose a year later were evaluated. Antibody responses to the vaccine strain and heterologous strains (non-vaccine-type strains) and the persistence of these antibodies were measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay up to 1 year after the last dose. The proportion of subjects with SBA titers of ≥4 against the vaccine strain increased from 3% prevaccination to 65% after the third dose. Ten months later, this proportion had declined to 28%. The fourth dose induced a booster response demonstrated by 93% of subjects achieving a titer of ≥4. One year after the booster dose, 64% still showed SBA titers of ≥4. Cross-reacting antibodies were induced against all heterologous strains tested, although the magnitude of SBA titers differed widely between the different strains. All four doses of MenBvac were safe. Both MenBvac and the placebo had reactogenicity profiles of mild to moderate local and systemic reactions. Pain, the most common reaction, was reported with similar frequencies in both groups. No serious adverse events occurred in the MenBvac group. This study confirmed the good immunogenicity of the primary course of MenBvac and demonstrated prolonged persistence and increased cross-reactivity of functional antibodies elicited by a booster dose.
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interlaboratory standardization of the measurement of serum bactericidal activity by using human complement against meningococcal serogroup b strain 44 76 sl before and after vaccination with the norwegian menbvac outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2005Co-Authors: Ray Borrow, Arne E Hoiby, Philipp Oster, Einar Rosenqvist, Ingeborg S Aaberge, George F Santos, Lynn T Eudey, Anne Glennie, Jamie Findlow, Paul BalmerAbstract:There is currently no standardized serum bactericidal antibody (SBA) assay for evaluating immune responses to meningococcal outer Membrane Vesicle or protein vaccines. Four laboratories, Manchester Health Protection Agency (MC HPA), New Zealand Institute of Environmental Science and Research Limited (NZ ESR), Norwegian Institute of Public Health (NIPH), and Chiron Vaccines (Chiron), measured SBA titers in the same panel of human sera (n = 76) from laboratory staff (n = 21) vaccinated with MenBvac. Blood samples were collected prevaccination, prior to each of the three doses of MenBvac given at 6-week intervals, and 6 weeks following the third dose. Initial results showed a number of discrepancies in results between the four participating laboratories. The greatest effect on titers appeared to be due to differences among laboratories in the maintenance of the meningococcal serogroup B test strain, 44/76-SL. A repeat study was conducted using the same frozen isolate (meningococcal serogroup B test strain 44/76-SL), freshly distributed to all four laboratories. Using SBA titers from the tilt method for all samples, and using MC HPA as the comparator, the results were as follows for NZ ESR, NIPH, and Chiron, respectively, using log10 titers: correlation coefficients (r) were 0.966, 0.967, and 0.936; intercepts were 0.08, 0.15, and 0.17; and slopes were 0.930, 0.851, and 0.891. In both prevaccination and postvaccination samples from 15 subjects assayed by all four laboratories, similar increases in SBA (fourfold or greater) were observed (for 11, 11, 9, and 9 subjects for MC HPA, NZ ESR, NIPH, and Chiron, respectively), and similar percentages of subjects with SBA titers of ≥4 prevaccination and 6 weeks following each dose were found. The SBA assay has been harmonized between the four different laboratories with good agreement on seroconversion rates, n-fold changes in titers, and percentages of subjects with SBA titers of ≥4.
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the concept of tailor made protein based outer Membrane Vesicle vaccines against meningococcal disease
Vaccine, 2005Co-Authors: Johan Holst, Berit Feiring, Lisbeth Meyer Naess, Gunnstein Norheim, Paul A Kristiansen, Arne E Hoiby, Klaus Bryn, Philipp Oster, Paolo Costantino, Muhamed-kheir TahaAbstract:Protein-based, outer Membrane Vesicle (OMV) vaccines have previously proven to be efficacious against serogroup B meningococcal disease in Norway and Cuba. Currently, a public health intervention is going on in order to control a serogroup B epidemic in New Zealand. The scale-up and standardization of vaccine production required for controlling the New Zealand epidemic has allowed the establishment of large-scale GMP manufacturing for OMV vaccines. The outcome of this will be licensing of the vaccine in New Zealand and possibly other countries. The availability of licensed OMV vaccines raises the question of whether such vaccines may provide the opportunity to control other outbreaks and epidemics. For instance, such a vaccine could control a localised outbreak of group B meningococci in Normandy, France. "Tailor-made" vaccines, focusing on the sub-capsular antigens may also be considered for use in sub-Saharan Africa for the prevention of the recurrent outbreaks by serogroups A and W135 meningococci. This assumption is based on the epidemiological observation that meningococcal outbreaks in Africa are clonal and are strikingly stable regarding their phenotypic characteristics.
Valérie Delbos - One of the best experts on this subject based on the ideXlab platform.
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Impact of MenBvac, an outer Membrane Vesicle (OMV) vaccine, on the meningococcal carriage.
Vaccine, 2013Co-Authors: Valérie Delbos, Muhamed-kheir Taha, Ludovic Lemée, Jacques Benichou, Gilles Berthelot, Ala-eddine Deghmane, Jean-philippe Leroy, Estelle Houivet, Eva Hong, François CaronAbstract:The aim of the study was to analyze the impact of MenBvac, an outer Membrane Vesicle (OMV) vaccine against P1.7,16 strains, on meningococcal carriage. During a B:14:P1.7,16/ST-32 outbreak in Normandy (France), children aged 1-7 years were randomly selected to participate in the study. Among the 1082 volunteers, there were 17 Neisseria meningitidis carriers (carriage rate of 1.57%). MenBvac vaccination appeared associated with lower carriage rate, i.e., 0.31% among the vaccinated children versus 2.10% among the non-vaccinated (p=0.03). The beneficial effect on carriage was observed regardless of the strain serogroup. OMV-vaccinated mice also showed reduction of bacterial acquisition of OMV-homolog and hererolog strains in respiratory pathways after intranasal challenge. These results suggest that meningococcal OMV-based vaccines reduce meningococcal carriage and may hence confer herd immunity.
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Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer Membrane Vesicle vaccine MenBvac.
Vaccine, 2012Co-Authors: François Caron, Valérie Delbos, Jacques Benichou, Ala-eddine Deghmane, Jean-philippe Leroy, Estelle Houivet, Eva Hong, Muhamed-kheir TahaAbstract:A meningococcal B:14:P1.7,16 outbreak in Normandy (France) was recently controlled using MenBvac, an outer Membrane Vesicle vaccine previously designed against the B:15:P1.7,16 strain. The further emergence of a new B:14:P1.7,16 outbreak in another district in Normandy led us to explore immunity against B:14:P1.7,16 before and after the MenBvac campaign using a 2+1 (day 0, week 6, month 8) schedule. Children (1-5 years) were sampled before, during and up to one year after vaccination. Serum bactericidal activity against B:14:P1.7,16 was titrated using human complement (hSBA) and immune response was defined by hSBA titer ≥4 as a surrogate for protection. The percentage of hSBA titer ≥4 was 10.8% before vaccination, raised to 84.1% 6 weeks after the completion of the schedule, but declined to 39.7% one year later. This level is lower than the targeted 60% level and suggests only short-term persistence of response against B:14:P1.7,16 using this schedule.
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From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak.
The Lancet Infectious Diseases, 2011Co-Authors: François Caron, Jean-philippe Leroy, Isabelle Du Châtelet, Corinne Ruckly, Myriam Blanchard, Nicole Bohic, Nathalie Massy, Isabelle Morer, Daniel Floret, Valérie DelbosAbstract:BACKGROUND: Outer-Membrane-Vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop. We studied the use of already available vaccine to control an outbreak caused by a genetically close strain. METHODS: From 2006 to 2009, all individuals younger than 20 years living in the region of Normandy, France, in which an outbreak caused by a B:14:P1.7,16 strain occurred, were eligible to receive MenBvac, a Norwegian vaccine designed 20 years earlier against a strain sharing the same serosubtype (B:15:P1.7,16). The immunogenicity (in a randomly selected cohort of 400 children aged 1-5 years), safety, and epidemiological effect of the vaccination were assessed. FINDINGS: 26,014 individuals were eligible to receive the vaccine. Shortage of vaccine production prompted start of the campaign in the highest incidence groups (1-5 years). 16,709 (64%) received a complete vaccination schedule of whom 13,589 (81%) received a 2+1 dose schedule (week 0, week 6, and month 8). At 6 weeks after the third dose, of 235 vaccinees for whom samples were available, 206 (88%) had a seroresponse, and 108 (56 %) of 193 had a seroresponse at 15 months. These results were similar to those described for tailor-made vaccines and their homologous strain. Only previously described adverse effects occurred. The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period (from 31·6 per 100,000 to 5·9 per 100,000; p=0·001). INTERPRETATION: The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close. Other meningococcal B clonal outbreaks might benefit from this strategy; and previously described outer-Membrane-Vesicle vaccines can be effective against various strains.
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from tailor made to ready to wear meningococcal b vaccines longitudinal study of a clonal meningococcal b outbreak
Lancet Infectious Diseases, 2011Co-Authors: F Caron, Jean-philippe Leroy, Isabelle Du Châtelet, Corinne Ruckly, Myriam Blanchard, Nicole Bohic, Nathalie Massy, Isabelle Morer, Daniel Floret, Valérie DelbosAbstract:Summary Background Outer-Membrane-Vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop. We studied the use of already available vaccine to control an outbreak caused by a genetically close strain. Methods From 2006 to 2009, all individuals younger than 20 years living in the region of Normandy, France, in which an outbreak caused by a B:14:P1.7,16 strain occurred, were eligible to receive MenBvac, a Norwegian vaccine designed 20 years earlier against a strain sharing the same serosubtype (B:15:P1.7,16). The immunogenicity (in a randomly selected cohort of 400 children aged 1–5 years), safety, and epidemiological effect of the vaccination were assessed. Findings 26 014 individuals were eligible to receive the vaccine. Shortage of vaccine production prompted start of the campaign in the highest incidence groups (1–5 years). 16 709 (64%) received a complete vaccination schedule of whom 13 589 (81%) received a 2+1 dose schedule (week 0, week 6, and month 8). At 6 weeks after the third dose, of 235 vaccinees for whom samples were available, 206 (88%) had a seroresponse, and 108 (56 %) of 193 had a seroresponse at 15 months. These results were similar to those described for tailor-made vaccines and their homologous strain. Only previously described adverse effects occurred. The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period (from 31·6 per 100 000 to 5·9 per 100 000; p=0·001). Interpretation The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close. Other meningococcal B clonal outbreaks might benefit from this strategy; and previously described outer-Membrane-Vesicle vaccines can be effective against various strains. Funding French Ministry of Health.
Arne E Hoiby - One of the best experts on this subject based on the ideXlab platform.
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characterization of meningococcal serogroup b outer Membrane Vesicle vaccines from strain 44 76 after growth in different media
Vaccine, 2010Co-Authors: Nikos Tsolakos, Paul A Kristiansen, Arne E Hoiby, Kristian Lie, Karin Bolstad, Sarah Maslen, Amanda Wallington, Caroline Vipond, Mark SkehelAbstract:In this study, we evaluated the effect of the growth medium on the composition and immunogenicity of meningococcal outer Membrane Vesicle (OMV) vaccines after cultivation of the Norwegian serogroup B 44/76 vaccine strain in either Frantz’ or modified Catlin-6 media (MC.6M). Differential proteomic analysis revealed that 97% of the OMV proteins maintained the same levels in the two preparations. However, a number of differentially expressed proteins, including TdfH, OpcA, OMP NMB0088, hypothetical NMB2134, lipoprotein NMB1126/1164 and NspA, increased significantly in OMVs produced from bacteria grown in the MC.6M. Together with increased lipopolysaccharide levels, the increased expression of these proteins was associated with significantly higher serum bactericidal titres in mice immunized with the MC.6M OMV vaccine. The high resolution two-dimensional separation of the OMVs on a large-format gel across a pH range of 3–11 resolved around 2000 protein spots from which 75 proteins were identified by mass spectrometry.
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interlaboratory standardization of the measurement of serum bactericidal activity by using human complement against meningococcal serogroup b strain 44 76 sl before and after vaccination with the norwegian menbvac outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2005Co-Authors: Ray Borrow, Arne E Hoiby, Philipp Oster, Einar Rosenqvist, Ingeborg S Aaberge, George F Santos, Lynn T Eudey, Anne Glennie, Jamie Findlow, Paul BalmerAbstract:There is currently no standardized serum bactericidal antibody (SBA) assay for evaluating immune responses to meningococcal outer Membrane Vesicle or protein vaccines. Four laboratories, Manchester Health Protection Agency (MC HPA), New Zealand Institute of Environmental Science and Research Limited (NZ ESR), Norwegian Institute of Public Health (NIPH), and Chiron Vaccines (Chiron), measured SBA titers in the same panel of human sera (n = 76) from laboratory staff (n = 21) vaccinated with MenBvac. Blood samples were collected prevaccination, prior to each of the three doses of MenBvac given at 6-week intervals, and 6 weeks following the third dose. Initial results showed a number of discrepancies in results between the four participating laboratories. The greatest effect on titers appeared to be due to differences among laboratories in the maintenance of the meningococcal serogroup B test strain, 44/76-SL. A repeat study was conducted using the same frozen isolate (meningococcal serogroup B test strain 44/76-SL), freshly distributed to all four laboratories. Using SBA titers from the tilt method for all samples, and using MC HPA as the comparator, the results were as follows for NZ ESR, NIPH, and Chiron, respectively, using log10 titers: correlation coefficients (r) were 0.966, 0.967, and 0.936; intercepts were 0.08, 0.15, and 0.17; and slopes were 0.930, 0.851, and 0.891. In both prevaccination and postvaccination samples from 15 subjects assayed by all four laboratories, similar increases in SBA (fourfold or greater) were observed (for 11, 11, 9, and 9 subjects for MC HPA, NZ ESR, NIPH, and Chiron, respectively), and similar percentages of subjects with SBA titers of ≥4 prevaccination and 6 weeks following each dose were found. The SBA assay has been harmonized between the four different laboratories with good agreement on seroconversion rates, n-fold changes in titers, and percentages of subjects with SBA titers of ≥4.
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the concept of tailor made protein based outer Membrane Vesicle vaccines against meningococcal disease
Vaccine, 2005Co-Authors: Johan Holst, Berit Feiring, Lisbeth Meyer Naess, Gunnstein Norheim, Paul A Kristiansen, Arne E Hoiby, Klaus Bryn, Philipp Oster, Paolo Costantino, Muhamed-kheir TahaAbstract:Protein-based, outer Membrane Vesicle (OMV) vaccines have previously proven to be efficacious against serogroup B meningococcal disease in Norway and Cuba. Currently, a public health intervention is going on in order to control a serogroup B epidemic in New Zealand. The scale-up and standardization of vaccine production required for controlling the New Zealand epidemic has allowed the establishment of large-scale GMP manufacturing for OMV vaccines. The outcome of this will be licensing of the vaccine in New Zealand and possibly other countries. The availability of licensed OMV vaccines raises the question of whether such vaccines may provide the opportunity to control other outbreaks and epidemics. For instance, such a vaccine could control a localised outbreak of group B meningococci in Normandy, France. "Tailor-made" vaccines, focusing on the sub-capsular antigens may also be considered for use in sub-Saharan Africa for the prevention of the recurrent outbreaks by serogroups A and W135 meningococci. This assumption is based on the epidemiological observation that meningococcal outbreaks in Africa are clonal and are strikingly stable regarding their phenotypic characteristics.
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functional activities and epitope specificity of human and murine antibodies against the class 4 outer Membrane protein rmp of neisseria meningitidis
Infection and Immunity, 1999Co-Authors: Einar Rosenqvist, Arne E Hoiby, Elisabeth Wedege, Audun Aase, Alexis Musacchio, Ellen Namork, Jan Kolberg, Alexei A Delvig, Rolf Dalseg, Terje E MichaelsenAbstract:Antibodies against the class 4 outer Membrane protein (OMP) from Neisseria meningitidis have been purified from sera from vaccinees immunized with the Norwegian meningococcal group B outer Membrane Vesicle vaccine. The human sera and purified antibodies reacted strongly with the class 4 OMP in immunoblots, whereas experiments with whole bacteria showed only weak reactions, indicating that the antibodies mainly reacted with parts of the class 4 molecule that were not exposed. The purified human anti-class 4 OMP antibodies and the monoclonal antibodies (MAbs) were neither bactericidal nor opsonic against live meningococci. Three new MAbs against the class 4 OMP were generated and compared with other, previously described MAbs. Three linear epitopes in different regions of the class 4 OMP were identified by the reaction of MAbs with synthetic peptides. The MAbs showed no blocking effect on bactericidal activity of MAbs against other OMPs. However, one of the eight purified human anti-class 4 OMP antibody preparations, selected from immunoblot reactions among sera from 27 vaccinees, inhibited at high concentrations the bactericidal effect of a MAb against the class 1 OMP. However, these antibodies were not vaccine induced, as they were present also before vaccination. Therefore, this study gave no evidence that vaccination with a meningococcal outer Membrane Vesicle vaccine containing the class 4 OMP induces blocking antibodies. Our data indicated that the structure of class 4 OMP does not correspond to standard β-barrel structures of integral OMPs and that no substantial portion of the OmpA-like C-terminal region of this protein is located at the surface of the outer Membrane.
Einar Rosenqvist - One of the best experts on this subject based on the ideXlab platform.
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functional and specific antibody responses in adult volunteers in new zealand who were given one of two different meningococcal serogroup b outer Membrane Vesicle vaccines
Clinical and Vaccine Immunology, 2007Co-Authors: Elisabeth Wedege, Philipp Oster, Karin Bolstad, Einar Rosenqvist, Audun Aase, Tove Karin Herstad, Lisa Mccallum, Diana R MartinAbstract:This study presents detailed analyses of total and specific serum antibody levels among 26 and 24 adult volunteers before vaccination and after the third dose of the meningococcal serogroup B outer Membrane Vesicle (OMV) vaccines MeNZB and MenBvac, respectively, in a clinical trial in New Zealand (V. Thornton, D. Lennon, K. Rasanathan, J. O’Hallahan, P. Oster, J. Stewart, S. Tilman, I. Aaberge, B. Feiring, H. Nokleby, E. Rosenqvist, K. White, S. Reid, K. Mulholland, M. J. Wakefield, and D. Martin, Vaccine 24:1395‐1400, 2006). With the homologous vaccine strains as targets, both vaccines induced significant increases in serum bactericidal and opsonophagocytic activities and in the levels of immunoglobulin G (IgG) to OMV antigens in an enzyme-linked immunosorbent assay (ELISA) and to live meningococci by flow cytometry. They also induced high levels of activity against the heterologous strains, particularly in terms of opsonophagocytic activity and IgG binding to live bacteria. The antibody levels with the homologous and heterologous strains in the four assays showed high and significant positive correlations. Specific IgG binding to 10 major OMV antigens in each vaccine was measured by scanning of immunoblots; ELISAs for two antigens, lipopolysaccharide and Neisseria surface protein A (NspA), were also performed. Both vaccines elicited significant increases in IgG binding to all homologous and heterologous OMV antigens except NspA. The total IgG band intensity on the blots correlated significantly with the IgG levels determined by the OMV ELISA and flow cytometry. In conclusion, the results of the various immunological assays showed that both OMV vaccines gave rise to high levels of specific and cross-reacting antibodies. Since 1991, an epidemic of meningococcal disease in New Zealand has caused over 200 deaths and nearly 6,000 cases of disease in a population of 4 million people (www.moh.govt.nz). Most of the cases are caused by serogroup B strains, and from 1991 through 2004, 86% of these expressed the P1.7-2,4 (P1.7b,4) PorA and belonged to the sequence type 41/44 complex (lineage III) (13, 15). The majority of these strains also expressed the serotype 4 PorB protein (14). In contrast to the other capsular meningococcal polysaccharides, group B polysaccharide is poorly immunogenic in humans (65); and vaccines based on subcapsular antigens, such as outer Membrane proteins or outer Membrane Vesicles (OMVs) from various group B strains, have been developed and used in clinical trials (6, 9, 12, 18, 48). The experience of the Norwegian Institute of Public Health (NIPH) with the development and production of the OMV vaccine (MenBvac) for the protection trial in Norway (6, 19) led to a partnership with Chiron Vaccines (now Novartis Vaccines & Diagnostics) and the New Zealand Ministry of Health, in which NIPH developed and produced a tailor-made OMV vaccine (MeNZB) from a representative strain of the New Zealand epidemic (NZ98/254)
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persisting immune responses indicating long term protection after booster dose with meningococcal group b outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2006Co-Authors: Berit Feiring, Philipp Oster, Jan Fuglesang, Lisbeth M Naess, Oddveig S Helland, Sandrine Tilman, Einar Rosenqvist, Marianne Riise A Bergsaker, Hanne Nokleby, Ingeborg S AabergeAbstract:MenBvac is an outer Membrane Vesicle vaccine against systemic meningococcal disease caused by serogroup B Neisseria meningitidis. In this placebo-controlled double-blind study including 374 healthy adolescents, the safety and immunogenicity of a schedule of three primary doses 6 weeks apart followed by a fourth dose a year later were evaluated. Antibody responses to the vaccine strain and heterologous strains (non-vaccine-type strains) and the persistence of these antibodies were measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay up to 1 year after the last dose. The proportion of subjects with SBA titers of ≥4 against the vaccine strain increased from 3% prevaccination to 65% after the third dose. Ten months later, this proportion had declined to 28%. The fourth dose induced a booster response demonstrated by 93% of subjects achieving a titer of ≥4. One year after the booster dose, 64% still showed SBA titers of ≥4. Cross-reacting antibodies were induced against all heterologous strains tested, although the magnitude of SBA titers differed widely between the different strains. All four doses of MenBvac were safe. Both MenBvac and the placebo had reactogenicity profiles of mild to moderate local and systemic reactions. Pain, the most common reaction, was reported with similar frequencies in both groups. No serious adverse events occurred in the MenBvac group. This study confirmed the good immunogenicity of the primary course of MenBvac and demonstrated prolonged persistence and increased cross-reactivity of functional antibodies elicited by a booster dose.
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interlaboratory standardization of the measurement of serum bactericidal activity by using human complement against meningococcal serogroup b strain 44 76 sl before and after vaccination with the norwegian menbvac outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2005Co-Authors: Ray Borrow, Arne E Hoiby, Philipp Oster, Einar Rosenqvist, Ingeborg S Aaberge, George F Santos, Lynn T Eudey, Anne Glennie, Jamie Findlow, Paul BalmerAbstract:There is currently no standardized serum bactericidal antibody (SBA) assay for evaluating immune responses to meningococcal outer Membrane Vesicle or protein vaccines. Four laboratories, Manchester Health Protection Agency (MC HPA), New Zealand Institute of Environmental Science and Research Limited (NZ ESR), Norwegian Institute of Public Health (NIPH), and Chiron Vaccines (Chiron), measured SBA titers in the same panel of human sera (n = 76) from laboratory staff (n = 21) vaccinated with MenBvac. Blood samples were collected prevaccination, prior to each of the three doses of MenBvac given at 6-week intervals, and 6 weeks following the third dose. Initial results showed a number of discrepancies in results between the four participating laboratories. The greatest effect on titers appeared to be due to differences among laboratories in the maintenance of the meningococcal serogroup B test strain, 44/76-SL. A repeat study was conducted using the same frozen isolate (meningococcal serogroup B test strain 44/76-SL), freshly distributed to all four laboratories. Using SBA titers from the tilt method for all samples, and using MC HPA as the comparator, the results were as follows for NZ ESR, NIPH, and Chiron, respectively, using log10 titers: correlation coefficients (r) were 0.966, 0.967, and 0.936; intercepts were 0.08, 0.15, and 0.17; and slopes were 0.930, 0.851, and 0.891. In both prevaccination and postvaccination samples from 15 subjects assayed by all four laboratories, similar increases in SBA (fourfold or greater) were observed (for 11, 11, 9, and 9 subjects for MC HPA, NZ ESR, NIPH, and Chiron, respectively), and similar percentages of subjects with SBA titers of ≥4 prevaccination and 6 weeks following each dose were found. The SBA assay has been harmonized between the four different laboratories with good agreement on seroconversion rates, n-fold changes in titers, and percentages of subjects with SBA titers of ≥4.
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serum bactericidal activity correlates with the vaccine efficacy of outer Membrane Vesicle vaccines against neisseria meningitidis serogroup b disease
Vaccine, 2003Co-Authors: Johan Holst, Berit Feiring, Hanne Nokleby, Ingeborg S Aaberge, J E Fuglesang, E A Hoiby, Einar RosenqvistAbstract:For evaluation of serum bactericidal activity (SBA) as surrogate for the efficacy of outer Membrane Vesicle (OMV) vaccines against Neisseria meningitidis serogroup B disease, we have reanalyzed data from a randomized double blind placebo-controlled efficacy trial involving 172000 secondary school students (aged 13-14 years) in Norway (1988-1991). A cohort of the efficacy trial consisting of 880 individuals was selected for immunogenicity studies. An efficacy of 87% was calculated for a 10-month observation period. However, after an observation period of 29 months, the estimated efficacy against group B disease induced by vaccination was 57%. The immunogenicity study showed that the SBA geometric mean titer (GMT) for the vaccinees was 2.4 before vaccination and 19.0 six weeks after the second vaccine dose. One year after vaccination the GMT was reduced to 2.8. A separate three-dose study with 304 adolescents showed that with a third dose at 10 months after the second dose (i.e. when cases of disease started to appear) a strong booster response was induced. Ten months after the second dose the SBA was reduced to near pre-immunization level. Following the third dose the SBA geometric mean titer of 2.7 increased to 62.3. One year after the third dose, the GMT was markedly higher than 6 weeks after the second dose (12.6 versus 8.8). Thus, protection after vaccination corresponds with the level of SBA. In order to reach lasting protective levels of SBA in a population, three vaccine doses are probably required. Measurements of SBA are likely to be useful for evaluating various upcoming formulations and improvements of immunization regimens for OMV vaccines.
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outer Membrane protein Vesicle vaccines for meningococcal disease
Methods in molecular medicine, 2001Co-Authors: Carl E Frasch, Johan Holst, Loek Van Alphen, Jan Poolman, Einar RosenqvistAbstract:Alternative strategies exist for prevention of group B Neisseria meningitidis (meningococcal) disease through vaccination (see Chapters 5 , 8 , 13 , 14 in this volume). However, the most promising approach to date has been the use of outer-Membrane Vesicle (OMV) vaccines for induction of bactericidal antibodies against cell-surface outer-Membrane proteins (OMPs).
Ingeborg S Aaberge - One of the best experts on this subject based on the ideXlab platform.
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immunogenicity and safety of a combination of two serogroup b meningococcal outer Membrane Vesicle vaccines
Clinical and Vaccine Immunology, 2007Co-Authors: Synne Sandbu, Berit Feiring, Lisbeth Meyer Naess, Philipp Oster, Oddveig S Helland, Ingeborg S Aaberge, Audun Aase, Hilde Bakke, Annecathrine Kristoffersen, Kjersti M RydlandAbstract: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 μg), MeNZB (25 μg), or the MenBvac and MeNZB (doses of 12.5 μg 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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persisting immune responses indicating long term protection after booster dose with meningococcal group b outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2006Co-Authors: Berit Feiring, Philipp Oster, Jan Fuglesang, Lisbeth M Naess, Oddveig S Helland, Sandrine Tilman, Einar Rosenqvist, Marianne Riise A Bergsaker, Hanne Nokleby, Ingeborg S AabergeAbstract:MenBvac is an outer Membrane Vesicle vaccine against systemic meningococcal disease caused by serogroup B Neisseria meningitidis. In this placebo-controlled double-blind study including 374 healthy adolescents, the safety and immunogenicity of a schedule of three primary doses 6 weeks apart followed by a fourth dose a year later were evaluated. Antibody responses to the vaccine strain and heterologous strains (non-vaccine-type strains) and the persistence of these antibodies were measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay up to 1 year after the last dose. The proportion of subjects with SBA titers of ≥4 against the vaccine strain increased from 3% prevaccination to 65% after the third dose. Ten months later, this proportion had declined to 28%. The fourth dose induced a booster response demonstrated by 93% of subjects achieving a titer of ≥4. One year after the booster dose, 64% still showed SBA titers of ≥4. Cross-reacting antibodies were induced against all heterologous strains tested, although the magnitude of SBA titers differed widely between the different strains. All four doses of MenBvac were safe. Both MenBvac and the placebo had reactogenicity profiles of mild to moderate local and systemic reactions. Pain, the most common reaction, was reported with similar frequencies in both groups. No serious adverse events occurred in the MenBvac group. This study confirmed the good immunogenicity of the primary course of MenBvac and demonstrated prolonged persistence and increased cross-reactivity of functional antibodies elicited by a booster dose.
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interlaboratory standardization of the measurement of serum bactericidal activity by using human complement against meningococcal serogroup b strain 44 76 sl before and after vaccination with the norwegian menbvac outer Membrane Vesicle vaccine
Clinical and Vaccine Immunology, 2005Co-Authors: Ray Borrow, Arne E Hoiby, Philipp Oster, Einar Rosenqvist, Ingeborg S Aaberge, George F Santos, Lynn T Eudey, Anne Glennie, Jamie Findlow, Paul BalmerAbstract:There is currently no standardized serum bactericidal antibody (SBA) assay for evaluating immune responses to meningococcal outer Membrane Vesicle or protein vaccines. Four laboratories, Manchester Health Protection Agency (MC HPA), New Zealand Institute of Environmental Science and Research Limited (NZ ESR), Norwegian Institute of Public Health (NIPH), and Chiron Vaccines (Chiron), measured SBA titers in the same panel of human sera (n = 76) from laboratory staff (n = 21) vaccinated with MenBvac. Blood samples were collected prevaccination, prior to each of the three doses of MenBvac given at 6-week intervals, and 6 weeks following the third dose. Initial results showed a number of discrepancies in results between the four participating laboratories. The greatest effect on titers appeared to be due to differences among laboratories in the maintenance of the meningococcal serogroup B test strain, 44/76-SL. A repeat study was conducted using the same frozen isolate (meningococcal serogroup B test strain 44/76-SL), freshly distributed to all four laboratories. Using SBA titers from the tilt method for all samples, and using MC HPA as the comparator, the results were as follows for NZ ESR, NIPH, and Chiron, respectively, using log10 titers: correlation coefficients (r) were 0.966, 0.967, and 0.936; intercepts were 0.08, 0.15, and 0.17; and slopes were 0.930, 0.851, and 0.891. In both prevaccination and postvaccination samples from 15 subjects assayed by all four laboratories, similar increases in SBA (fourfold or greater) were observed (for 11, 11, 9, and 9 subjects for MC HPA, NZ ESR, NIPH, and Chiron, respectively), and similar percentages of subjects with SBA titers of ≥4 prevaccination and 6 weeks following each dose were found. The SBA assay has been harmonized between the four different laboratories with good agreement on seroconversion rates, n-fold changes in titers, and percentages of subjects with SBA titers of ≥4.
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serum bactericidal activity correlates with the vaccine efficacy of outer Membrane Vesicle vaccines against neisseria meningitidis serogroup b disease
Vaccine, 2003Co-Authors: Johan Holst, Berit Feiring, Hanne Nokleby, Ingeborg S Aaberge, J E Fuglesang, E A Hoiby, Einar RosenqvistAbstract:For evaluation of serum bactericidal activity (SBA) as surrogate for the efficacy of outer Membrane Vesicle (OMV) vaccines against Neisseria meningitidis serogroup B disease, we have reanalyzed data from a randomized double blind placebo-controlled efficacy trial involving 172000 secondary school students (aged 13-14 years) in Norway (1988-1991). A cohort of the efficacy trial consisting of 880 individuals was selected for immunogenicity studies. An efficacy of 87% was calculated for a 10-month observation period. However, after an observation period of 29 months, the estimated efficacy against group B disease induced by vaccination was 57%. The immunogenicity study showed that the SBA geometric mean titer (GMT) for the vaccinees was 2.4 before vaccination and 19.0 six weeks after the second vaccine dose. One year after vaccination the GMT was reduced to 2.8. A separate three-dose study with 304 adolescents showed that with a third dose at 10 months after the second dose (i.e. when cases of disease started to appear) a strong booster response was induced. Ten months after the second dose the SBA was reduced to near pre-immunization level. Following the third dose the SBA geometric mean titer of 2.7 increased to 62.3. One year after the third dose, the GMT was markedly higher than 6 weeks after the second dose (12.6 versus 8.8). Thus, protection after vaccination corresponds with the level of SBA. In order to reach lasting protective levels of SBA in a population, three vaccine doses are probably required. Measurements of SBA are likely to be useful for evaluating various upcoming formulations and improvements of immunization regimens for OMV vaccines.