scholarly journals Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens

2018 ◽  
Vol 3 ◽  
pp. 151 ◽  
Author(s):  
Charlene M. C. Rodrigues ◽  
Hannah Chan ◽  
Caroline Vipond ◽  
Keith Jolley ◽  
Odile B. Harrison ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Membrane Vesicles ◽  
Shotgun Proteomics ◽  
Outer Membrane Vesicles ◽  
Amino Acid Sequences ◽  
Protein Antigens ◽  
Structured Population ◽  
Vaccine Antigens ◽  
Successful Approach

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, has 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:Here, 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 thePubMLST.org/neisseriadatabase 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 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.

scholarly journals Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens

2019 ◽  
Vol 3 ◽  
pp. 151 ◽  
Author(s):  
Charlene M. C. Rodrigues ◽  
Hannah Chan ◽  
Caroline Vipond ◽  
Keith Jolley ◽  
Odile B. Harrison ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Membrane Vesicles ◽  
Shotgun Proteomics ◽  
Outer Membrane Vesicles ◽  
Amino Acid Sequences ◽  
Protein Antigens ◽  
Structured Population ◽  
Vaccine Antigens ◽  
Successful Approach

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 thePubMLST.org/neisseriadatabase 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.

scholarly journals Decoration of Outer Membrane Vesicles with Multiple Antigens by Using an Autotransporter Approach

2014 ◽  
Vol 80 (18) ◽  
pp. 5854-5865 ◽  
Author(s):  
Maria H. Daleke-Schermerhorn ◽  
Tristan Felix ◽  
Zora Soprova ◽  
Corinne M. ten Hagen-Jongman ◽  
David Vikström ◽  
...  
Keyword(s):  
Immune Responses ◽  
Outer Membrane ◽  
Vaccine Development ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Heterologous Proteins ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Heterologous Antigens

ABSTRACTOuter membrane vesicles (OMVs) are spherical nanoparticles that naturally shed from Gram-negative bacteria. They are rich in immunostimulatory proteins and lipopolysaccharide but do not replicate, which increases their safety profile and renders them attractive vaccine vectors. By packaging foreign polypeptides in OMVs, specific immune responses can be raised toward heterologous antigens in the context of an intrinsic adjuvant. Antigens exposed at the vesicle surface have been suggested to elicit protection superior to that from antigens concealed inside OMVs, but hitherto robust methods for targeting heterologous proteins to the OMV surface have been lacking. We have exploited our previously developed hemoglobin protease (Hbp) autotransporter platform for display of heterologous polypeptides at the OMV surface. One, two, or three of theMycobacterium tuberculosisantigens ESAT6, Ag85B, and Rv2660c were targeted to the surface ofEscherichia coliOMVs upon fusion to Hbp. Furthermore, a hypervesiculating ΔtolRΔtolAderivative of attenuatedSalmonella entericaserovar Typhimurium SL3261 was generated, enabling efficient release and purification of OMVs decorated with multiple heterologous antigens, exemplified by theM. tuberculosisantigens and epitopes fromChlamydia trachomatismajor outer membrane protein (MOMP). Also, we showed that delivery ofSalmonellaOMVs displaying Ag85B to antigen-presenting cellsin vitroresults in processing and presentation of an epitope that is functionally recognized by Ag85B-specific T cell hybridomas. In conclusion, the Hbp platform mediates efficient display of (multiple) heterologous antigens, individually or combined within one molecule, at the surface of OMVs. Detection of antigen-specific immune responses upon vesicle-mediated delivery demonstrated the potential of our system for vaccine development.

Immuno-proteomics analysis between OMV of vaccine and dominant wild type strains of Bordetella pertussis in Iran

2020 ◽  
Author(s):  
Ali Badamchi ◽  
Fariborz Bahrami ◽  
Alireza Hadizadeh Tasbiti ◽  
Shamsi Yari ◽  
Morvarid Shafiei ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Protein Profile ◽  
Protein Composition ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Cell Vaccine ◽  
Wild Type ◽  
Protein Antigens ◽  
Vaccination Programs ◽  
Type Strains

Background and Objectives: Despite widespread vaccination programs against pertussis, there has been a worldwide re- surgence of the disease in recent years. We aimed to investigate protein composition of outer membrane vesicles (OMV) of Bordetella pertussis (Bp) and to evaluate the immunogenicity of OMV antigens both in the vaccine and the dominant wild type strains in Iran. Materials and Methods: The OMV were purified from both vaccine and wild type strains. The immunoreactivity of the OMVs was investigated by exposing sera taken from the patients and the vaccinated infants. The protein profiles of OMVs were compared using two-dimensional electrophoresis. The LC-MS/MS was used to analyse and identify differentially ex- pressed protein spots. Results: The two type strains showed differences in their 2D gel protein profile. Further analysis of selected proteins from the dominant Iranian strains using LC-MS/MS demonstrated that the identified proteins fell into different functional catego- ries including (i) metabolism, (ii) membrane transport and secretion system, (iii) biosynthesis and degradation, (iv) adaption, adhesion, pathogenicity, conserved hypothetical and protection responses. Moreover, a number of immunogenic proteins were identified including Bp 2434 (serine protease) and Bp 1616 (putative DNA binding protein) from the vaccine and the wild type strains, respectively which could be considered as potential antigens for an OMV vaccine. Conclusion: OMV Bp could be considered as an alternative vaccine against pertussis, containing the bacterium’s protein antigens that can confer equal efficacy compared to a whole bacterial cell vaccine with advantages such as less side effects and lower costs than acellular pertussis vaccines.

scholarly journals Expression of Heterologous Antigens in Commensal Neisseria spp.: Preservation of Conformational Epitopes with Vaccine Potential

2004 ◽  
Vol 72 (11) ◽  
pp. 6511-6518 ◽  
Author(s):  
Clíona A. O'Dwyer ◽  
Karen Reddin ◽  
Denis Martin ◽  
Stephen C. Taylor ◽  
Andrew R. Gorringe ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Meningococcal Disease ◽  
Protective Efficacy ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Heterologous Proteins ◽  
Protein Vaccine ◽  
Native Conformation ◽  
Protein Antigens

ABSTRACT Commensal neisseriae share with Neisseria meningitidis (meningococcus) a tendency towards overproduction of the bacterial outer envelope, leading to the formation and release during growth of outer membrane vesicles (OMVs). OMVs from both meningococci and commensal neisseriae have shown promise as vaccines to protect against meningococcal disease. We report here the successful expression at high levels of heterologous proteins in commensal neisseriae and the display, in its native conformation, of one meningococcal outer membrane protein vaccine candidate, NspA, in OMVs prepared from such a recombinant Neisseria flavescens strain. These NspA-containing OMVs conferred protection against otherwise lethal intraperitoneal challenge of mice with N. meningitidis serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen. This development promises to facilitate the design of novel vaccines containing membrane protein antigens that are otherwise difficult to present in native conformation that provide cross-protective efficacy in the prevention of meningococcal disease.

scholarly journals Natural and engineered bacterial outer membrane vesicles

2019 ◽  
Vol 5 (4) ◽  
pp. 184-198 ◽  
Author(s):  
Guangchao Qing ◽  
Ningqiang Gong ◽  
Xiaohui Chen ◽  
Jing Chen ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Vaccine Development ◽  
Rapid Development ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Bacterial Outer Membrane ◽  
Biomedical Field ◽  
Biomedical Fields

Abstract Bacterial outer membrane vesicle (OMV) is a kind of spherical lipid bilayer nanostructure naturally secreted by bacteria, which has diverse functions such as intracellular and extracellular communication, horizontal gene transfer, transfer of contents to host cells, and eliciting an immune response in host cells. In this review, several methods including ultracentrifugation and precipitation for isolating OMVs were summarized. The latest progresses of OMVs in biomedical fields, especially in vaccine development, cancer treatment, infection control, and bioimaging and detection were also summarized in this review. We highlighted the importance of genetic engineering for the safe and effective application and in facilitating the rapid development of OMVs. Finally, we discussed the bottleneck problems about OMVs in preparation and application at present and put forward our own suggestions about them. Some perspectives of OMVs in biomedical field were also provided.

scholarly journals Sequential Immunization with Vesicles Prepared from Heterologous Neisseria meningitidis Strains Elicits Broadly Protective Serum Antibodies to Group B Strains

2002 ◽  
Vol 70 (11) ◽  
pp. 6021-6031 ◽  
Author(s):  
Gregory R. Moe ◽  
Patricia Zuno-Mitchell ◽  
Samantha N. Hammond ◽  
Dan M. Granoff
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Protein A ◽  
Surface Protein ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Novel Approach ◽  
Bactericidal Antibody ◽  
Porin Proteins ◽  
Group B

ABSTRACT The capsular polysaccharide of Neisseria meningitidis group B is an autoantigen, whereas noncapsular antigens are highly variable. These factors present formidable challenges for development of a broadly protective and safe group B vaccine. Mice and guinea pigs were sequentially immunized with three doses of micovesicles or outer membrane vesicles prepared from three meningococcal strains that were each antigenically heterologous with respect to the two major porin proteins, PorA and PorB, and the group capsular polysaccharide. The resulting antisera conferred passive protection against meningococcal group B bacteremia in infant rats and elicited complement-mediated bactericidal activity against genetically diverse group B strains that were either homologous or heterologous with respect to PorA of the strains used to prepare the vaccine. By using knockout strains, a portion of the bactericidal antibody was directed against the highly conserved protein, neisserial surface protein A (NspA). Further, an anti-NspA monoclonal antibody elicited by the sequential immunization was highly bactericidal against strains that were previously shown to be resistant to bacteriolysis by anti-NspA antibodies produced by immunization with recombinant NspA. Sequential immunization with heterologous vesicle preparations offers a novel approach to eliciting broadly protective immunity against N. meningitidis strains. An NspA-based vaccine prepared from protein expressed by Neisseria also may be more effective than the corresponding recombinant protein made in Escherichia coli.

scholarly journals ZnuD, a Potential Candidate for a Simple and Universal Neisseria meningitidis Vaccine

2013 ◽  
Vol 81 (6) ◽  
pp. 1915-1927 ◽  
Author(s):  
Kerstin Hubert ◽  
Nathalie Devos ◽  
Ines Mordhorst ◽  
Christine Tans ◽  
Guy Baudoux ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Age Groups ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Potential Candidate ◽  
Content Type ◽  
Homologous Protein ◽  
Vaccine Antigens ◽  
Type Strains

ABSTRACTNeisseria meningitidisserogroup B (MenB) is a major cause of bacterial sepsis and meningitis, with the highest disease burden in young children. Available vaccines are based on outer membrane vesicles (OMVs) obtained from wild-type strains. However, particularly in toddlers and infants, they confer protection mostly against strains expressing the homologous protein PorA, a major and variable outer membrane protein. In the quest for alternative vaccine antigens able to provide broad MenB strain coverage in younger populations, but potentially also across all age groups, ZnuD, a protein expressed under zinc-limiting conditions, may be considered a promising candidate. Here, we have investigated the potential value of ZnuD and show that it is a conserved antigen expressed by all MenB strains tested except for some strains of clonal complex ST-8. In mice and guinea pigs immunized with ZnuD-expressing OMVs, antibodies were elicited that were able to trigger complement-mediated killing of all the MenB strains and serogroup A, C, and Y strains tested when grown under conditions of zinc limitation. ZnuD is also expressed during infection, since anti-ZnuD antibodies were detected in sera from patients. In conclusion, we confirm the potential of ZnuD-bearing OMVs as a component of an effective MenB vaccine.

scholarly journals Outer Membrane Vesicle Induction and Isolation for Vaccine Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Melanie D. Balhuizen ◽  
Edwin J. A. Veldhuizen ◽  
Henk P. Haagsman
Keyword(s):  
Outer Membrane ◽  
Vaccine Development ◽  
Current Knowledge ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Gram Negative Bacteria ◽  
Bacterial Surface ◽  
Advantages And Disadvantages ◽  
Isolation Methods

Gram-negative bacteria release vesicular structures from their outer membrane, so called outer membrane vesicles (OMVs). OMVs have a variety of functions such as waste disposal, communication, and antigen or toxin delivery. These vesicles are the promising structures for vaccine development since OMVs carry many surface antigens that are identical to the bacterial surface. However, isolation is often difficult and results in low yields. Several methods to enhance OMV yield exist, but these do affect the resulting OMVs. In this review, our current knowledge about OMVs will be presented. Different methods to induce OMVs will be reviewed and their advantages and disadvantages will be discussed. The effects of the induction and isolation methods used in several immunological studies on OMVs will be compared. Finally, the challenges for OMV-based vaccine development will be examined and one example of a successful OMV-based vaccine will be presented.

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