ARTICLE OPEN OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans
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ABSTRACT:
ORGANISM(S): Mus musculus Neisseria meningitidis
PROVIDER: GSE224291 | GEO | 2023/04/12
REPOSITORIES: GEO
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Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the OMV component of 4CMenB vaccine in infant sera before and after vaccination
2023-04-15 | GSE224340 | GEO
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults.
2020-08-28 | GSE152785 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-04-12 | GSE224348 | GEO
Project description:Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.
| S-EPMC7536418 | biostudies-literature
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
2021-10-13 | E-MTAB-11084 | biostudies-arrayexpress
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
2021-10-29 | E-MTAB-11117 | biostudies-arrayexpress
Project description:Vaccines to prevent capsular group B meningococcal disease have been based on proteins, as the polysaccharide capsule was deemed unsuitable due to its similarity to human tissues. Outer membrane vesicle (OMV) vaccines have been targeted at specific capsular group B epidemics in Cuba, Norway, and New Zealand, with the major immunogen determined as porin A (PorA). Subcapsular protein vaccines aim to increase breadth of coverage of meningococcal strains, by the inclusion of protein variants from many different clonal complexes (ccs). Using scalable and portable genomic techniques, it is possible to study the diversity of OMV and subcapsular proteins in relevant meningococcal populations. Shotgun proteomics identified 461 proteins in the OMVs derived from NZ98/254, a component of the Bexsero® vaccine, with a complex proteome comprised of outer membrane proteins and proteins from other cellular compartments. Amino acid sequences for 24 selected proteins were catalogued within the PubMLST Neisseria database as part of the OMV peptide Typing (OMVT) scheme. Of the 24 proteins included, there was variation in the extent of diversity and association with ccs from the most conserved peptides FbpA (NEISp0578) and putative periplasmic proteins (NEISp1063) to the most diverse TbpA (NEISp1690). There were 1752 OMVTs identified amongst 2492/3506 isolates. OMVTs were further grouped into clusters (identical at ≥18 peptide sequences), 45.3% of isolates were assigned to one of 27 OMVT clusters. Both OMVTs and clusters were strongly associated with cc, genogroup and recombinant Bexsero® antigens. The OMVT scheme represents an open-access, web-based tool for the systematic analysis of the multiple components of OMV vaccines, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with both genogroup and Bexsero® Antigen Sequence type (BAST). This highly structured population of disease-causing meningococci is consistent with proposed effects of host immune selection and competition between allelic variants on meningococcal population structure. This has implications for future vaccine assessment, and development, especially the choice of antigen combinations. The methodology is portable and will facilitate region-specific WGS interrogation, allowing informed choices about vaccine development or implementation.
2018-11-14 | PXD011622 | Pride
Project description:Neisseria meningitidis is a major cause of endemic cases and epidemics of meningitis and devastating septicemia. Although effective vaccines exist for several serogroups of pathogenic N. meningitidis, conventional vaccinology approaches have failed to provide a universal solution for serogroup B (MenB) which consequently remains an important burden of disease worldwide. The advent of whole-genome sequencing changed the approach to vaccine development, enabling the identification of potential vaccine candidates starting directly with the genomic information, with a process named reverse vaccinology. The application of reverse vaccinology to MenB allowed the identification of new protein antigens able to induce bactericidal antibodies. Three highly immunogenic antigens (fHbp, NadA and NHBA) were combined with outer membrane vesicles and formulated for human use in a multicomponent vaccine, named 4CMenB. This is the first MenB vaccine based on recombinant proteins able to elicit a robust bactericidal immune response in adults, adolescents and infants against a broad range of serogroup B isolates. This review describes the successful story of the development of the 4CMenB vaccine, with particular emphasis on the functional, immunological and structural characterization of the protein antigens included in the vaccine.
| S-EPMC3360877 | biostudies-literature
Project description:The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV or aOMV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV had the ability to confer cross-protection against different bacterial strain. Next, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections
2023-07-20 | PXD033690 | Pride
Project description:IntroductionInvasive meningococcal disease (IMD) is an important public health concern. In developed countries, most IMD is caused by meningococcal serogroup B (MenB) and two protein-based MenB vaccines are currently available: the four-component vaccine 4CMenB (Bexsero, GSK) and the bivalent vaccine MenB-FHbp (Trumenba, Pfizer). Genes encoding the 4CMenB vaccine antigens are also present in strains belonging to other meningococcal serogroups.MethodsTo evaluate the potential of 4CMenB vaccination to protect adolescents against non-MenB IMD, we tested the bactericidal activity of sera from immunized adolescents on 147 (127 European and 20 Brazilian) non-MenB IMD isolates, with a serum bactericidal antibody assay using human complement (hSBA). Serum pools were prepared using samples from randomly selected participants in various clinical trials, pre- and post-vaccination: 12 adolescents who received two doses of 4CMenB 2 months apart, and 10 adolescents who received a single dose of a MenACWY conjugate vaccine (as positive control).Results4CMenB pre-immune sera killed 7.5% of the 147 non-MenB isolates at hSBA titers ≥ 1:4. In total, 91 (61.9%) tested isolates were killed by post-dose 2 pooled sera at hSBA titers ≥ 1:4, corresponding to 44/80 (55.0%) MenC, 26/35 (74.3%) MenW, and 21/32 (65.6%) MenY isolates killed.Conclusion4CMenB vaccination in adolescents induces bactericidal killing of non-MenB isolates, suggesting that mass vaccination could impact IMD due to serogroups other than MenB.
| S-EPMC7954916 | biostudies-literature