Immunogenicity of Two Efficacious Outer Membrane Protein‐Based Serogroup B Meningococcal Vaccines among Young Adults in Iceland

Perkins, Bradley A.; Jónsdóttir, Kristín; Briem, Haraldur; Griffiths, Elwyn; Plikaytis, Brian D.; Høiby, E. Arne; Rosenqvist, Einar; Holst, Johan; Nøkleby, Hanne; Sotolongo, Franklin; Sierra, Gustavo; Campa, H. C.; Carlone, George M.; Williams, D. R.; Dykes, Janet K.; Kapczynski, Darrell R.; Tikhomirov, E; Wenger, Jay D.; Broome, Claire V.

doi:10.1086/514232

Cited by 153 publications

(124 citation statements)

References 11 publications

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“…Three studies have examined the effect of MenB OMV vaccines on carriage; in Chile [77], Norway [78] and Iceland [79], high vaccine coverage had no effect on rates of meningococcal carriage. A large study in the UK of nearly 3000 young adults immunized with 4CMenB and/or quadravalent meningococcal A, C, W135, Y conjugate vaccines is examining the effect on rates of meningococcal carriage [104].…”

Section: Carriage and Herd Immunitymentioning

confidence: 99%

Controlling serogroup B invasive meningococcal disease: the Canadian perspective

Bettinger¹,

Deeks²,

Halperin³

et al. 2013

Expert Review of Vaccines

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Section: Carriage and Herd Immunitymentioning

confidence: 99%

Controlling serogroup B invasive meningococcal disease: the Canadian perspective

Bettinger¹,

Deeks²,

Halperin³

et al. 2013

Expert Review of Vaccines

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“…The Men-B vaccines that have been most extensively investigated in human clinical trials are based on multiple subcapsular surface Ags in which porin A (PorA), a class 1 outer membrane protein (OMP), appears to be a dominant immunogen (20 -24). These include two partially purified Men-B OMP vaccines, developed by the Finlay Institute in Cuba and the National Institute of Public Health in Norway, that are presented as proteoliposome vesicles adsorbed onto aluminum hydroxide (21,22,25), and an outer membrane vesicle (OMV) hexavalent vaccine developed at the Netherlands Institute of Public Health and the Environment (Rijksinstituut voor Volksgezondheid & Milieu), derived from two recombinant strains each expressing three different PorA proteins (23). Although these vaccines have been shown to engender a 50 -80% protective efficacy, this has frequently been found to be strain specific, variable in infants under 18 mo of age, and of limited longevity (20).…”

mentioning

confidence: 99%

“…Depending on the nature of the T cell help, contact with Ag at a mucosal surface can either lead to a predominantly proinflammatory Th1-type response, an Ab-associated Th2 response (29), or, in the absence of danger signal, tolerance (31,32). It is unclear whether meningococcal carriage results in immunological priming or immune unresponsiveness, as with microbial colonizers at other mucosal sites and to what extent mucosal cellular immunity accounts for the disparity between the levels of SBA and protective immunity observed in vaccine trials (22,33) In this study, we aimed to ascertain whether T cell-mediated immunological memory to N. meningitidis is located at the mucosal level, to characterize the nature of this response, and to determine its relationship to circulating humoral immunity.…”

mentioning

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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“…Experimental OMV vaccines have undergone phase III trials in humans (3,4,11,31) and have been shown to produce limited protection in adults (3). However, the immune responses were of limited duration (32), and no protection was shown in children under 2 years of age, the group at greatest risk of infection (11,28).…”

mentioning

confidence: 99%

Immunization with the Recombinant PorB Outer Membrane Protein Induces a Bactericidal Immune Response against Neisseria meningitidis

et al. 2002

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Infections with Neisseria meningitidis are characterized by life-threatening meningitis and septicemia. The meningococcal porin proteins from serogroup B meningococci have been identified as candidates for inclusion in vaccines to prevent such infections. In this study, we investigated the vaccine potential of the PorB porin protein free of other meningococcal components. The porB gene from a strain of Neisseria meningitidis expressing the class 3 outer membrane porin protein (PorB3) was cloned into the pRSETB vector, and the protein was expressed at high levels in a heterologous host Escherichia coli. The recombinant protein was purified to homogeneity by affinity chromatography and used for immunization after incorporation into liposomes and into micelles composed either of zwitterionic detergent or nondetergent sulfobetaine. The immunogenicity of these preparations was compared to recombinant PorB protein adsorbed to Al(OH) 3 adjuvant as a control. Although sera raised against the protein adsorbed to Al(OH) 3 reacted with the purified recombinant protein, sera raised against liposomes and micelles showed greater activity with native protein, as measured by enzyme immunoassay with outer membranes and by whole-cell immunofluorescence. Reactivity with native protein was considerably enhanced by incorporation of the adjuvant monophosphoryl lipid A into the liposome or micelle preparations. Recognition of the native protein was in a serotype-specific manner and was associated with the ability of the antisera to promote high levels of serotype-specific complement-mediated killing of meningococci. These results demonstrate that the PorB protein should be considered as a component of a vaccine designed to prevent serogroup B meningococcal infection.

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Immunogenicity of Two Efficacious Outer Membrane Protein‐Based Serogroup B Meningococcal Vaccines among Young Adults in Iceland

Cited by 153 publications

References 11 publications

Controlling serogroup B invasive meningococcal disease: the Canadian perspective

Controlling serogroup B invasive meningococcal disease: the Canadian perspective

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

Immunization with the Recombinant PorB Outer Membrane Protein Induces a Bactericidal Immune Response against Neisseria meningitidis

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