Production, characterization and control of a Neisseria meningitidis hexavalent class 1 outer membrane protein containing vesicle vaccine

Claassen, Ivo; Meylis, J; Ley, Peter van der; Peeters, Cacha; Brons, H.J.; Robert, Jolanda; Borsboom, Dominique J.M.; Ark, Arno van der; Straaten, Ineke van; Roholl, P. J. M.; Kuipers, Betsy; Poolman, Jan

doi:10.1016/0264-410x(96)00020-5

Cited by 159 publications

(125 citation statements)

References 24 publications

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“…Vaccines directed against the serogrouping antigen, the capsular polysaccharide, are effective against some meningococci (Gotschlich et al, 1969;Jennings & Lugowski, 1981), but poor immunological reactivity and immunological similarity to host antigens has hampered the development of such vaccines against serogroup B meningococci, which are responsible for most disease in Europe, North and South America and Australasia (Finne et al, 1983;Reingold et al, 1985;Wyle et al, 1972). Outer-membrane proteins (OMPs) are major candidates in the search for alternative vaccine components either in purified form (Boslego et al, 1995) or as part of complex outer-membrane vesicle (OMV) formulations (Bjune et al, 1991;Claassen et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 fetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VR). A nomenclature system for the peptides encoded by the VR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component.

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Section: Introductionmentioning

confidence: 99%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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“…OMVs are nanoscale (∼100 nm) proteoliposomes that constitutively bud from the outer membrane of Gram-negative bacteria (13,14), and they contain components derived from the bacterial outer membrane and periplasm. In contrast to synthetic particulate systems, these OMV vaccines represent a unique system where the antigen and delivery vehicle together are derived from the Neisseria meningitidis pathogen itself (15,16). The proven safety and efficacy records of these OMV vaccines, particularly in The Netherlands (17) and in Norway (12,18), together with the knowledge that vesicles are produced by nearly all species of Gram-negative bacteria (including Escherichia coli), present the possibility of employing OMVs for the delivery of recombinant protein antigens.…”

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confidence: 99%

Delivery of foreign antigens by engineered outer membrane vesicle vaccines

Chen

Osterrieder

Metzger

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

256

247

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As new disease threats arise and existing pathogens grow resistant to conventional interventions, attention increasingly focuses on the development of vaccines to induce protective immune responses. Given their admirable safety records, protein subunit vaccines are attractive for widespread immunization, but their disadvantages include poor immunogenicity and expensive manufacture. We show here that engineered Escherichia coli outer membrane vesicles (OMVs) are an easily purified vaccine-delivery system capable of greatly enhancing the immunogenicity of a low-immunogenicity protein antigen without added adjuvants. Using green-fluorescent protein (GFP) as the model subunit antigen, genetic fusion of GFP with the bacterial hemolysin ClyA resulted in a chimeric protein that elicited strong anti-GFP antibody titers in immunized mice, whereas immunization with GFP alone did not elicit such titers. Harnessing the specific secretion of ClyA to OMVs, the ClyA-GFP fusion was found localized in OMVs, resulting in engineered recombinant OMVs. The anti-GFP humoral response in mice immunized with the engineered OMV formulations was indistinguishable from the response to the purified ClyA-GFP fusion protein alone and equal to purified proteins absorbed to aluminum hydroxide, a standard adjuvant. In a major improvement over current practice, engineered OMVs containing ClyA-GFP were easily isolated by ultracentrifugation, effectively eliminating the need for laborious antigen purification from cell-culture expression systems. With the diverse collection of heterologous proteins that can be functionally localized with OMVs when fused with ClyA, this work signals the possibility of OMVs as a robust and tunable technology platform for a new generation of prophylactic and therapeutic vaccines.protein subunit | adjuvant

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“…Two vaccines for serogroup-B meningococcal disease currently exist that are formulations comprising bacterial surface antigens that have been naturally incorporated into OMVs (Oster et al, 2005), (Feiring et al , 2006). These OMVbased vaccines represent a novel system where both the antigen and delivery vehicle are derived from the Neisseria meningitidis pathogen itself (Claassen et al, 1996), (Arigita et al, 2004). Moreover, genetically engineered OMVs offer an attractive possibility for use as easily purified vaccine-delivery systems capable of greatly enhancing the immunogenicity of lowimmunogenicity protein antigens without the need for an added adjuvant.…”

Section: Vaccinesmentioning

confidence: 99%