Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine

Morán, Elizabeth; Burden, Robert; Labrie, Joseph E.; Wen, Zhiping; Wang, Xinmin; Zollinger, Wendell D.; Zhang, Lan; Pinto, Valerian B.

doi:10.1128/cvi.00070-12

Cited by 17 publications

(10 citation statements)

References 30 publications

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“…The mutations include lpxL1 inactivation (reducing endotoxicity), deletion of synX , stabilization of high expression OpcA, insertion of a second porA (P1.22,14) and insertion of a second copy of fHbpv.1 [44]. Studies in mice suggests that the vaccine may provide protection against other serogroups [95,96].…”

Section: Further Developments In Serogroup B Meningococcal Disease Prmentioning

confidence: 99%

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

Martin¹,

Snape

2013

Expert Review of Vaccines

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The first meningococcal vaccine with the potential to provide broad coverage against serogroup B disease has recently been approved for use in Europe. This vaccine, multi-component serogroup B vaccine (4CMenB), contains recombinant proteins and outer membrane vesicles, and has been extensively studied in clinical trials involving over 7500 adults, children and infants. As well as demonstrating immunogenicity against a range of serogroup B meningococcal strains, these trials have also demonstrated relatively high rates of fever following infant immunization. This article will summarize the vaccine composition, clinical trials and suggested schedules of this vaccine, with specific attention to immunogenicity, reactogenicity, safety, potential coverage and optimal implementation of this vaccine.

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Section: Further Developments In Serogroup B Meningococcal Disease Prmentioning

confidence: 99%

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

Martin¹,

Snape

2013

Expert Review of Vaccines

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show abstract

“…Colonization factors are also attractive vaccine targets due to their potential to induce antibodies that block the initial establishment of infection. While pilin, the major subunit of the gonococcal pilus, is too antigenically variable to be effective, PilQ, which is the pilus secretin and thereby essential for pilus function, is an attractive target because antibodies against meningococcal PilQ are bactericidal (196). The gonococcus expresses several other outer membrane proteins that mediate adherence and/or invasion of host cells.…”

Section: Recent Vaccination Effortsmentioning

confidence: 99%

Progress Toward a Gonococcal Vaccine: The Way Forward

2019

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The concept of immunizing against gonorrhea has received renewed interest because of the recent emergence of strains of Neisseria gonorrhoeae that are resistant to most currently available antibiotics, an occurrence that threatens to render gonorrhea untreatable. However, despite efforts over many decades, no vaccine has yet been successfully developed for human use, leading to pessimism over whether this goal was actually attainable. Several factors have contributed to this situation, including extensive variation of the expression and specificity of many of the gonococcal surface antigens, and the ability of N. gonorrhoeae to resist destruction by complement and other innate immune defense mechanisms. The natural host restriction of N. gonorrhoeae for humans, coupled with the absence of any definable state of immunity arising from an episode of gonorrhea, have also complicated efforts to study gonococcal pathogenesis and the host's immune responses. However, recent findings have elucidated how the gonococcus exploits and manipulates the host's immune system for its own benefit, utilizing human-specific receptors for attachment to and invasion of tissues, and subverting adaptive immune responses that might otherwise be capable of eliminating it. While no single experimental model is capable of providing all the answers, experiments utilizing human cells and tissues in vitro, various in vivo animal models, including genetically modified strains of mice, and both experimental and observational human clinical studies, have combined to yield important new insight into the immuno-pathogenesis of gonococcal infection. In turn, these have now led to novel approaches for the development of a gonococcal vaccine. Ongoing investigations utilizing all available tools are now poised to make the development of an effective human vaccine against gonorrhea an achievable goal within a foreseeable time-frame.

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“…The recently described NOMV vaccine has also been shown to be effective against other N meningitidis serogroups [18] . Further investigation on the vaccine revealed that LOS and PorA appear to be the major inducers of the bactericidal response [17] , [31] , of which the LOS appears to be broadly cross-protective. Based on those observations coupled with the observation that vaccines containing L2 and L3,7 LOS would possibly cover 80% of the pathogenic serogroup B N. meningitidis strains [20] , and that approximately 60% of the disease causing serogroup B N. meningitidis strains in the MLST database belong to either ST 41/44, ST-11 or ST32 MLST complex [21] , we developed a simple NOMV vaccine from strains H44/76, NZ9547 and B16B6 that contains the endogenous PorAs and LOS.…”

Section: Discussionmentioning

confidence: 99%

The Development of an Experimental Multiple Serogroups Vaccine for Neisseria meningitidis

et al. 2013

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A native outer membrane vesicles (NOMV) vaccine was developed from three antigenically diverse strains of Neisseria meningitidis that express the L1,8, L2, and L3,7 lipooligosaccharide (LOS) immunotypes, and whose synX, and lpxL1 genes were deleted.. Immunogenicity studies in mice showed that the vaccine induced bactericidal antibody against serogroups B, C, W, Y and X N. meningitidis strains. However, this experimental NOMV vaccine was not effective against serogroup A N. meningitidis strains. N. meningitidis capsular polysaccharide (PS) from serogroups A, C, W and Y were effective at inducing bactericidal antibody when conjugated to either tetanus toxoid or the fHbp1-fHbp2 fusion protein fHbp(1+2). The combination of the NOMV vaccine and the N. meningitidis serogroup A capsular polysaccharide (MAPS) protein conjugate was capable of inducing bactericidal antibodies against a limited number of N. meningitidis strains from serogroups A, B, C, W, Y and X tested in this study.

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Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine

Cited by 17 publications

References 30 publications

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

Progress Toward a Gonococcal Vaccine: The Way Forward

The Development of an Experimental Multiple Serogroups Vaccine for Neisseria meningitidis

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