Comparative evaluation of potential components for group B meningococcal vaccine by passive protection in the infant rat and in vitro bactericidal assay

Saukkonen, Kirsi; Leinonen, Maija; Abdillahi, H; Poolman, Jan

doi:10.1016/0264-410x(89)90194-1

Cited by 141 publications

(82 citation statements)

References 18 publications

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“…This was supported by the immunological reactivities of the polyclonal mouse sera generated with the fetA mutant meningococci. Most of the reactivity of the four adsorbed sera could be ascribed to the FetA protein, specifically to the VR, and the results of these experiments were similar to those previously obtained for the PorA VRs, which contain epitopes recognized by the immune systems of both animal models and humans (Rosenqvist et al, 1995;Saukkonen et al, 1987).…”

Section: Discussionsupporting

confidence: 82%

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: Discussionsupporting

confidence: 82%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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“…In this study, we focused predominantly on PorA, a major meningococcal OMP which forms the basis of meningococcal classification or serosubtyping (65,66) and a candidate vaccine Ag which is capable of inducing SBA (67,68) and eliciting T cell immunity (24,69). A greater variation in responses was observed against the less common U.K. serosubtypes (TR10 and H44/76) and a higher prevalence of memory-type responses with the most common U.K. serosubtype (TR4; data not shown).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Davenport

Guthrie

Findlow

et al. 2003

The Journal of Immunology

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Naturally acquired protective immunity against Neisseria meningitidis is thought to partially explain the disparity between the high levels of carriage in the human nasopharynx and the rare incidence of disease. To investigate this immunity to Neisseria meningitidis at the mucosal level, in vitro cellular responses to outer membrane vesicle preparations derived from this pathogen were examined using mononuclear cells from the palatine tonsils of adults and children. Characterization of these responses was achieved by depletion of CD45RA+, CD45RO+, and CD19+ populations and outer membrane vesicles derived from isogenic mutants expressing different serosubtypes of the major outer membrane protein, porin A (PorA), no PorA and membrane preparations from a mutant with no LPS (LpxA−). The magnitude of cellular proliferative responses against the outer membrane vesicles were strongly associated with age and were largely T cell mediated, involving both CD45RO+ and CD45RA+ T cell phenotypes. Responses were not dependent on LPS but consisted of both PorA cross-specific and non-PorA-dependent responses. Cellular immunity against Neisseria meningitidis was found to be frequently associated with systemic IgG Abs but was not associated with serum bactericidal Abs. For the first time our results demonstrate an age-associated acquisition of mucosal T effector/memory cell responses to Neisseria meningitidis. This mucosal cellular immunity can be present in the absence of serum bactericidal Abs, a classical marker of protective immunity.

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“…Porins, including the P2 porin of H. influenzae, have been used as immunogens that are actively and/or passively protective in subsequent challenge experiments (13,16,27,32). However, serotypic variation of these porins has limited their usefulness as vaccine candidates (13,16,35).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of a conserved porin protein from Helicobacter pylori

et al. 1995

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Helicobacter pylori is a causative agent of gastritis in humans and is correlated with gastric ulcer formation. Infections with this bacterium have proven difficult to treat with antimicrobial agents. To better understand how this bacterium transports compounds such as antimicrobial agents across its outer membrane, identification of porin proteins is important. We have recently identified a family of H. pylori porins (HopA to HopD) (M. M. Exner, P. Doig, T. J. Trust, and R. E. W. Hancock, Infect. Immun. 63:1567-1572, 1995). Here, we report on an unrelated porin species (HopE) from this bacterium. This protein had a apparent molecular mass of 31 kDa and was seen to form 50-and 90-kDa aggregates that were designated putative dimeric and trimeric forms, respectively. The protein was purified to homogeneity and, with a model planar lipid membrane system, was shown to act as a nonselective pore with a single channel conductance in 1.0 M KCl of 1.5 nS, similarly to other bacterial nonspecific porins. An internal peptide sequence of HopE shared homology with the P2 porin of Haemophilus influenzae. HopE was also shown to be antigenic in vivo as assessed by sera taken from H. pylori-infected individuals and was immunologically conserved with both patient sera and specific monoclonal antibodies. From these data, it appears that HopE is a major nonselective porin of H. pylori. The implications of these findings are discussed.

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Comparative evaluation of potential components for group B meningococcal vaccine by passive protection in the infant rat and in vitro bactericidal assay

Cited by 141 publications

References 18 publications

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Isolation and characterization of a conserved porin protein from Helicobacter pylori

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