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Andrew J. Pollard - One of the best experts on this subject based on the ideXlab platform.
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The next chapter for group B Meningococcal Vaccines.
Critical reviews in microbiology, 2017Co-Authors: N Y Wang, Andrew J. PollardAbstract:The majority of invasive Meningococcal disease (IMD) in the developed world is caused by capsular group B Neisseria meningitidis, however success with vaccination against organisms bearing this capsule has previously been restricted to control of geographically limited clonal outbreaks. As we enter a new era, with the first routine program underway to control endemic group B Meningococcal disease for infants in the UK, it is timely to review the key landmarks in group B vaccine development, and discuss the issues determining whether control of endemic group B disease will be achieved. Evidence of a reduction in carriage acquisition of invasive group B Meningococcal strains, after vaccination among adolescents, is imperative if routine immunization is to drive population control of disease beyond those who are vaccinated (i.e. through herd immunity). The need for multiple doses to generate a sufficiently protective response and reactogenicity remain significant problems with the new generation of Vaccines. Despite these limitations, early data from the UK indicate that new group B Meningococcal Vaccines have the potential to have a major impact on Meningococcal disease, and to provide new insight into how we might do better in the future.
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bcr repertoire sequencing different patterns of b cell activation after two Meningococcal Vaccines
Immunology and Cell Biology, 2015Co-Authors: Jacob D Galson, Andrew J. Pollard, M N Ramasamy, Elizabeth A Clutterbuck, Johannes Truck, Marton Munz, Anna Fowler, Vincenzo Cerundolo, Gerton Lunter, Dominic F KellyAbstract:Next-generation sequencing was used to investigate the B-cell receptor heavy chain transcript repertoire of different B-cell subsets (naive, marginal zone (MZ), immunoglobulin M (IgM) memory and IgG memory) at baseline, and of plasma cells (PCs) 7 days following administration of serogroup ACWY Meningococcal polysaccharide and protein-polysaccharide conjugate Vaccines. Baseline B-cell subsets could be distinguished from each other using a small number of repertoire properties (clonality, mutation from germline and complementarity-determining region 3 (CDR3) length) that were conserved between individuals. However, analyzing the CDR3 amino-acid sequence (which is particularly important for antigen binding) of the baseline subsets showed few sequences shared between individuals. In contrast, day 7 PCs demonstrated nearly 10-fold greater sequence sharing between individuals than the baseline subsets, consistent with the PCs being induced by the vaccine antigen and sharing specificity for a more limited range of epitopes. By annotating PC sequences based on IgG subclass usage and mutation, and also comparing them with the sequences of the baseline cell subsets, we were able to identify different signatures after the polysaccharide and conjugate Vaccines. PCs produced after conjugate vaccination were predominantly IgG1, and most related to IgG memory cells. In contrast, after polysaccharide vaccination, the PCs were predominantly IgG2, less mutated and were equally likely to be related to MZ, IgM memory or IgG memory cells. High-throughput B-cell repertoire sequencing thus provides a unique insight into patterns of B-cell activation not possible from more conventional measures of immunogenicity.
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randomized clinical trial to evaluate the immunogenicity of quadrivalent Meningococcal conjugate and polysaccharide Vaccines in adults in the united kingdom
Clinical and Vaccine Immunology, 2014Co-Authors: M N Ramasamy, Matthew D. Snape, Elizabeth A Clutterbuck, Kathryn Haworth, Jaclyn Bowman, Omar Omar, Amber J Thompson, Geraldine Blanchardrohner, Andrew J. PollardAbstract:Meningococcal conjugate Vaccines are today successfully deployed in universal programs for children and adolescents in different geographic regions to control meningitis and septicemia. However, in adults, the advantages of these conjugates over the older polysaccharide Vaccines are less clear. In this randomized clinical trial, we demonstrated that both conjugate and polysaccharide quadrivalent Meningococcal Vaccines elicit protective antibody responses in adults aged 18 to 70. (This study has been registered at www.clinicaltrials.gov under registration no. NCT00901940.).
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serogroup b Meningococcal Vaccines an unfinished story
Lancet Infectious Diseases, 2010Co-Authors: Manish Sadarangani, Andrew J. PollardAbstract:Most invasive Meningococcal disease in developed countries is caused by Neisseria meningitidis with a serogroup B capsule. However, despite availability of Vaccines for other serogroups since the 1960s, no serogroup B vaccine exists. In this Review we look at the development of serogroup B Vaccines over the past 40 years. Outer membrane vesicle Vaccines have been successfully used to control geographically isolated epidemics, but most have not been highly immunogenic in young children or provided broad cross-protection from infections with other strains. Vaccines based on subcapsular antigens have recently produced promising results in early clinical trials, and the disease burden might be substantially reduced over the next few years.
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Meningococcal a c y and w 135 polysaccharide protein conjugate Vaccines
Archives of Disease in Childhood, 2007Co-Authors: David Pace, Andrew J. PollardAbstract:Serogroup C Meningococcal conjugate Vaccines, first launched in the UK in 1999, have been used successfully in Australia, Canada and several other European countries. Combination conjugate Vaccines, containing more than one Meningococcal polysaccharide, have been developed to broaden protection against the disease. A tetravalent Meningococcal A, C, Y and W-135 conjugate vaccine was licensed for use in 11-55 year old adolescents and adults in the US in January 2005, and subsequently also in 2-11 year old children in Canada in May 2006. This article discusses the different glycoconjugate Meningococcal Vaccines which have been developed and the potential for their use to control disease caused by serogroups A, C, Y and W-135 of Neisseria meningitidis.
Bradley A Perkins - One of the best experts on this subject based on the ideXlab platform.
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surveillance for Meningococcal disease and strategies for use of conjugate Meningococcal Vaccines in the united states
Vaccine, 2001Co-Authors: Jairam R Lingappa, Nancy E. Rosenstein, Elizabeth R Zell, Kathleen A Shutt, Anne Schuchat, Bradley A PerkinsAbstract:Abstract Background: Neisseria meningitidis is a leading cause of bacterial meningitis in US; new capsular type-specific conjugate Vaccines offer an opportunity for improved control of Meningococcal disease. We evaluated the relative burdens of invasive Meningococcal disease in US and examined the projected impact of various Meningococcal conjugate vaccination strategies on rates of Meningococcal disease. Methods: Meningococcal disease incidence rates were determined from active, population-based surveillance in selected US areas. Models were created to determine impact of vaccination of infants, toddlers, adolescents or college students with Meningococcal conjugate Vaccines, with assumptions for vaccine coverage, efficacy and duration of protection. Although we examined possible conjugate vaccine formulations including serogroups A, C, Y and W-135, the final vaccine impact analysis excluded serogroups A and W-135. Outcome measures were cumulative Meningococcal disease incidence, and incidence 10 years after initiating vaccination among 0–22-year-olds. Results: in models of serogroup C+Y Meningococcal conjugate vaccination of infants, toddlers and adolescents, the cumulative incidence of Meningococcal disease was reduced by 54, 48 and 25%, respectively; the toddler strategy had the greatest impact per dose. After 10 years of routine Meningococcal conjugate vaccination, Meningococcal disease could be reduced by 50% and deaths by 64%. Conclusions: use of Meningococcal conjugate vaccine could markedly reduce Meningococcal disease incidence. Our data, along with vaccine formulation and vaccination program considerations, will be important in determining the optimal choice of vaccination strategy.
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update on haemophilus influenzae serotype b and Meningococcal Vaccines
Pediatric Clinics of North America, 2000Co-Authors: Nancy E. Rosenstein, Bradley A PerkinsAbstract:HAEMOPHILUS INFLUENZA€ SEROTYPE b Before 1985, Huemophilus influenzae serotype b (Hib) was the most common cause of invasive bacterial disease in children less than 5 years of age in the United States, causing approximately 12,000 cases of bacterial meningitis and 7500 cases of other invasive Hib infections each yearzo Rates of Hib were highest among children less than 18 months of age; before 5 years of age, one in 200 children developed invasive Hib disease?O* 65 The case-fatality rate was 2% to 5%, and 15% to 30% of survivors of meningitis had hearing impairment or other neurologic sequelae?O The burden of illness caused by Hib made the development and use of effective Hib Vaccines a public health priority. The use of these Vaccines has resulted in the virtual elimination of Hib invasive disease among infants in only 10 years, which places this intervention among the most notable public health achievements of the past decade.18
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immunogenicity of two efficacious outer membrane protein based serogroup b Meningococcal Vaccines among young adults in iceland
The Journal of Infectious Diseases, 1998Co-Authors: Bradley A Perkins, Brian D. Plikaytis, Johan Holst, E. Arne Høiby, Kristin E Jonsdottir, H Briem, E Griffiths, Einar Rosenqvist, Hanne Nokleby, F SotolongoAbstract:Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B Meningococcal Vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B Meningococcal Vaccines.
Ian M. Feavers - One of the best experts on this subject based on the ideXlab platform.
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typing complex Meningococcal Vaccines to understand diversity and population structure of key vaccine antigens
Wellcome Open Research, 2018Co-Authors: Charlene M C Rodrigues, Ian M. Feavers, Caroline Vipond, Hannah Chan, Keith A Jolley, Odile B Harrison, Jun X Wheeler, Gail Whiting, Martin C J MaidenAbstract:Background: Protein-conjugate capsular polysaccharide Vaccines can potentially control invasive Meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups. Concerns raised by immunological similarity of the serogroup B capsule to human neural cell carbohydrates, meant that ‘serogroup B substitute’ Vaccines target more variable subcapsular protein antigens. A successful approach using outer membrane vesicles (OMVs) as major vaccine components had limited strain coverage. In 4CMenB (Bexsero ® ), recombinant proteins have been added to ameliorate this problem. Methods: Scalable, portable, genomic techniques were used to investigate the Bexsero ® OMV protein diversity in Meningococcal populations. Shotgun proteomics identified 461 proteins in the OMV, defining a complex proteome. Amino acid sequences for the 24 proteins most likely to be involved in cross-protective immune responses were catalogued within the PubMLST.org/neisseria database using a novel OMV peptide Typing (OMVT) scheme. Results: Among these proteins there was variation in the extent of diversity and association with Meningococcal lineages, identified as clonal complexes (ccs), ranging from the most conserved peptides (FbpA, NEISp0578, and putative periplasmic protein, NEISp1063) to the most diverse (TbpA, NEISp1690). There were 1752 unique OMVTs identified amongst 2492/3506 isolates examined by whole-genome sequencing (WGS). These OMVTs were grouped into clusters (sharing ≥18 identical OMVT peptides), with 45.3% of isolates assigned to one of 27 OMVT clusters. OMVTs and OMVT clusters were strongly associated with cc, genogroup, and Bexsero ® antigen variants, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with genogroup and Bexsero ® Antigen Sequence Type. This highly structured population of IMD-associated meningococci is consistent with strain structure models invoking host immune and/or metabolic selection. Conclusions: The OMVT scheme facilitates region-specific WGS investigation of Meningococcal diversity and is an open-access, portable tool with applications for vaccine development, especially in the choice of antigen combinations, assessment and implementation.
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History of Meningococcal Vaccines and their serological correlates of protection.
Vaccine, 2012Co-Authors: Caroline Vipond, Rory Care, Ian M. FeaversAbstract:For over a hundred years Neisseria meningitidis has been known to be one of the major causes of bacterial meningitis. However, effective Vaccines were not developed until the latter part of the 20th century. The first of these were based on purified high molecular weight capsular polysaccharides and more recently the development of glycoconjugate Vaccines has made paediatric immunisation programmes possible. The prevention of group B Meningococcal disease has remained a challenge throughout this period. This review charts the history of the development of Meningococcal Vaccines and the importance of serological correlates of protection in their evaluation.
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adjuvant properties of Meningococcal outer membrane vesicles and the use of adjuvants in neisseria meningitidis protein Vaccines
Expert Review of Vaccines, 2011Co-Authors: Holly Sanders, Ian M. FeaversAbstract:Efforts to develop a Meningococcal vaccine that will include coverage against serogroup B disease have largely focused on outer membrane protein antigens. The protection offered by currently licensed outer membrane vesicle (OMV) Vaccines is specific to epidemic strains as their immunodominant antigens are highly variable. Many new developmental Vaccines use multiple-antigen components to improve coverage, but these are often not very immunogenic without an effective adjuvant. In this article, some proposed mechanisms of adjuvant action are discussed, particularly with respect to use in developmental Meningococcal Vaccines. Many of these Vaccines use OMVs as vaccine components, and the inherent adjuvant properties of these vesicles will also be discussed. As few adjuvants are currently licensed for use in humans, and predicting clinical efficacy from preclinical investigations is difficult, it is likely that OMVs will continue to be used for their adjuvant properties in Meningococcal vaccine development in the near future.
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Meningococcal Vaccines and vaccine developments.
Methods in molecular medicine, 2001Co-Authors: Ian M. FeaversAbstract:Despite rapid advances in the diagnosis of bacterial infections and the availability of effective antibiotics, Meningococcal disease continues to represent a substantial public health problem for most countries (1-4). Disease usually develops rapidly, is notoriously difficult to distinguish from other febrile illnesses, and generally has a high case-fatality rate. The death of an otherwise fit and healthy individual can occur within a very short time from the first appearance of symptoms, those who survive frequently suffer from permanent tissue damage and neurological problems (4,5). Consequently, the development and implementation of effective immunoprophylaxis is a sine qua non for the comprehensive control of Meningococcal disease. From an historical perspective, many Meningococcal Vaccines have been developed and evaluated in clinical trials; unfortunately, no vaccine so far offers comprehensive protection. This overview traces the development of the existing licensed Vaccines and examines the prospects of vaccine candidates that are currently under development or subject to clinical evaluation.
Martin C J Maiden - One of the best experts on this subject based on the ideXlab platform.
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typing complex Meningococcal Vaccines to understand diversity and population structure of key vaccine antigens
Wellcome Open Research, 2018Co-Authors: Charlene M C Rodrigues, Ian M. Feavers, Caroline Vipond, Hannah Chan, Keith A Jolley, Odile B Harrison, Jun X Wheeler, Gail Whiting, Martin C J MaidenAbstract:Background: Protein-conjugate capsular polysaccharide Vaccines can potentially control invasive Meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups. Concerns raised by immunological similarity of the serogroup B capsule to human neural cell carbohydrates, meant that ‘serogroup B substitute’ Vaccines target more variable subcapsular protein antigens. A successful approach using outer membrane vesicles (OMVs) as major vaccine components had limited strain coverage. In 4CMenB (Bexsero ® ), recombinant proteins have been added to ameliorate this problem. Methods: Scalable, portable, genomic techniques were used to investigate the Bexsero ® OMV protein diversity in Meningococcal populations. Shotgun proteomics identified 461 proteins in the OMV, defining a complex proteome. Amino acid sequences for the 24 proteins most likely to be involved in cross-protective immune responses were catalogued within the PubMLST.org/neisseria database using a novel OMV peptide Typing (OMVT) scheme. Results: Among these proteins there was variation in the extent of diversity and association with Meningococcal lineages, identified as clonal complexes (ccs), ranging from the most conserved peptides (FbpA, NEISp0578, and putative periplasmic protein, NEISp1063) to the most diverse (TbpA, NEISp1690). There were 1752 unique OMVTs identified amongst 2492/3506 isolates examined by whole-genome sequencing (WGS). These OMVTs were grouped into clusters (sharing ≥18 identical OMVT peptides), with 45.3% of isolates assigned to one of 27 OMVT clusters. OMVTs and OMVT clusters were strongly associated with cc, genogroup, and Bexsero ® antigen variants, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with genogroup and Bexsero ® Antigen Sequence Type. This highly structured population of IMD-associated meningococci is consistent with strain structure models invoking host immune and/or metabolic selection. Conclusions: The OMVT scheme facilitates region-specific WGS investigation of Meningococcal diversity and is an open-access, portable tool with applications for vaccine development, especially in the choice of antigen combinations, assessment and implementation.
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Meningococcal Vaccines and herd immunity lessons learned from serogroup c conjugate vaccination programs
Expert Review of Vaccines, 2009Co-Authors: Caroline L Trotter, Martin C J MaidenAbstract:Effective Vaccines provide direct protection to immunized individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and thereby lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of Meningococcal serogroup C conjugate (MCC) Vaccines, with reductions in disease attack rates in unimmunized individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK, targeting teenagers for immunization was crucial in maximizing indirect effects, as most Meningococcal transmission occurs in this age group. Questions remain regarding the duration of herd protection and the most appropriate long-term immunization strategies. The magnitude of the herd effects following MCC vaccination was largely unanticipated, and has important consequences for the design and evaluation of new Meningococcal Vaccines.
Nancy E. Rosenstein - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of Serogroup A Meningococcal Vaccines in Africa: A Demonstration Project
Journal of health population and nutrition, 2004Co-Authors: Montse Soriano-gabarró, Nancy E. Rosenstein, F. Marc LaforceAbstract:Endemic and epidemic Meningococcal disease constitutes a major public-health problem in African countries of the 'meningitis belt' where incidence rates of the disease are many-fold higher (up to 25 cases per 100,000 population) than those in industrialized countries, and epidemics of Meningococcal disease occur with rates as high as 1,000 cases per 100,000 people. Using the precedent established during the licensing of conjugate Vaccines against Haemophilus influenzae type b and serogroup C meningococci and components of currently-licensed Meningococcal polysaccharide Vaccines, new Meningococcal conjugate Vaccines will likely be licensed using immunological endpoints as surrogates for clinical protection. Post-licensure evaluation of vaccine effectiveness will, therefore, be of increased importance. One vaccine being developed is the serogroup A Meningococcal (Men A) conjugate vaccine produced by the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization and the Program for Applied Technology in Health. This vaccine will likely be the first Meningococcal conjugate vaccine introduced on a large scale in Africa. This paper summarizes the general steps required for vaccine development, reviews the use of immunogenicity criteria as a licensing strategy for new Meningococcal Vaccines, and discusses plans for evaluating the impact of a Meningococcal A conjugate vaccine in Africa. Impact of this vaccine will be measured during a vaccine-demonstration project that will primarily measure the effectiveness of vaccine. Other studies will include evaluations of safety, vaccine coverage, impact on carriage and herd immunity, and prevention-effectiveness studies.
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surveillance for Meningococcal disease and strategies for use of conjugate Meningococcal Vaccines in the united states
Vaccine, 2001Co-Authors: Jairam R Lingappa, Nancy E. Rosenstein, Elizabeth R Zell, Kathleen A Shutt, Anne Schuchat, Bradley A PerkinsAbstract:Abstract Background: Neisseria meningitidis is a leading cause of bacterial meningitis in US; new capsular type-specific conjugate Vaccines offer an opportunity for improved control of Meningococcal disease. We evaluated the relative burdens of invasive Meningococcal disease in US and examined the projected impact of various Meningococcal conjugate vaccination strategies on rates of Meningococcal disease. Methods: Meningococcal disease incidence rates were determined from active, population-based surveillance in selected US areas. Models were created to determine impact of vaccination of infants, toddlers, adolescents or college students with Meningococcal conjugate Vaccines, with assumptions for vaccine coverage, efficacy and duration of protection. Although we examined possible conjugate vaccine formulations including serogroups A, C, Y and W-135, the final vaccine impact analysis excluded serogroups A and W-135. Outcome measures were cumulative Meningococcal disease incidence, and incidence 10 years after initiating vaccination among 0–22-year-olds. Results: in models of serogroup C+Y Meningococcal conjugate vaccination of infants, toddlers and adolescents, the cumulative incidence of Meningococcal disease was reduced by 54, 48 and 25%, respectively; the toddler strategy had the greatest impact per dose. After 10 years of routine Meningococcal conjugate vaccination, Meningococcal disease could be reduced by 50% and deaths by 64%. Conclusions: use of Meningococcal conjugate vaccine could markedly reduce Meningococcal disease incidence. Our data, along with vaccine formulation and vaccination program considerations, will be important in determining the optimal choice of vaccination strategy.
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update on haemophilus influenzae serotype b and Meningococcal Vaccines
Pediatric Clinics of North America, 2000Co-Authors: Nancy E. Rosenstein, Bradley A PerkinsAbstract:HAEMOPHILUS INFLUENZA€ SEROTYPE b Before 1985, Huemophilus influenzae serotype b (Hib) was the most common cause of invasive bacterial disease in children less than 5 years of age in the United States, causing approximately 12,000 cases of bacterial meningitis and 7500 cases of other invasive Hib infections each yearzo Rates of Hib were highest among children less than 18 months of age; before 5 years of age, one in 200 children developed invasive Hib disease?O* 65 The case-fatality rate was 2% to 5%, and 15% to 30% of survivors of meningitis had hearing impairment or other neurologic sequelae?O The burden of illness caused by Hib made the development and use of effective Hib Vaccines a public health priority. The use of these Vaccines has resulted in the virtual elimination of Hib invasive disease among infants in only 10 years, which places this intervention among the most notable public health achievements of the past decade.18