Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0
The threat from invasive meningococcal disease (IMD) remains a serious source of concern despite the licensure and availability of vaccines. A limitation of current serogroup B vaccines is the breadth of coverage afforded, resulting from the capacity for extensive variation of the meningococcus and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01621/full |
| _version_ | 1818889780244512768 |
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| author | Fadil A. Bidmos Simon Nadel Simon Nadel Gavin R. Screaton J. Simon Kroll Paul R. Langford |
| author_facet | Fadil A. Bidmos Simon Nadel Simon Nadel Gavin R. Screaton J. Simon Kroll Paul R. Langford |
| author_sort | Fadil A. Bidmos |
| collection | DOAJ |
| description | The threat from invasive meningococcal disease (IMD) remains a serious source of concern despite the licensure and availability of vaccines. A limitation of current serogroup B vaccines is the breadth of coverage afforded, resulting from the capacity for extensive variation of the meningococcus and its huge potential for the generation of further diversity. Thus, the continuous search for candidate antigens that will compose supplementary or replacement vaccines is mandated. Here, we describe successful efforts to utilize the reverse vaccinology 2.0 approach to identify novel functional meningococcal antigens. In this study, eight broadly cross-reactive sequence-specific antimeningococcal human monoclonal antibodies (hmAbs) were cloned from 4 ml of blood taken from a 7-month-old sufferer of IMD. Three of these hmAbs possessed human complement-dependent bactericidal activity against meningococcal serogroup B strains of disparate PorA and 4CMenB antigen sequence types, strongly suggesting that the target(s) of these bactericidal hmAbs are not PorA (the immunodominant meningococcal antigen), factor-H binding protein, or other components of current meningococcal vaccines. Reactivity of the bactericidal hmAbs was confirmed to a single ca. 35 kDa protein in western blots. Unequivocal identification of this antigen is currently ongoing. Collectively, our results provide proof-of-principle for the use of reverse vaccinology 2.0 as a powerful tool in the search for alternative meningococcal vaccine candidate antigens. |
| first_indexed | 2024-12-19T17:14:27Z |
| format | Article |
| id | doaj.art-8229d93971cd45d3b71b7bdd0387482f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T17:14:27Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8229d93971cd45d3b71b7bdd0387482f2022-12-21T20:12:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01621386461Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0Fadil A. Bidmos0Simon Nadel1Simon Nadel2Gavin R. Screaton3J. Simon Kroll4Paul R. Langford5Section of Paediatrics, Department of Medicine, Imperial College London, London, United KingdomSection of Paediatrics, Department of Medicine, Imperial College London, London, United KingdomSt. Mary’s Hospital, Paddington, London, United KingdomSection of Paediatrics, Department of Medicine, Imperial College London, London, United KingdomSection of Paediatrics, Department of Medicine, Imperial College London, London, United KingdomSection of Paediatrics, Department of Medicine, Imperial College London, London, United KingdomThe threat from invasive meningococcal disease (IMD) remains a serious source of concern despite the licensure and availability of vaccines. A limitation of current serogroup B vaccines is the breadth of coverage afforded, resulting from the capacity for extensive variation of the meningococcus and its huge potential for the generation of further diversity. Thus, the continuous search for candidate antigens that will compose supplementary or replacement vaccines is mandated. Here, we describe successful efforts to utilize the reverse vaccinology 2.0 approach to identify novel functional meningococcal antigens. In this study, eight broadly cross-reactive sequence-specific antimeningococcal human monoclonal antibodies (hmAbs) were cloned from 4 ml of blood taken from a 7-month-old sufferer of IMD. Three of these hmAbs possessed human complement-dependent bactericidal activity against meningococcal serogroup B strains of disparate PorA and 4CMenB antigen sequence types, strongly suggesting that the target(s) of these bactericidal hmAbs are not PorA (the immunodominant meningococcal antigen), factor-H binding protein, or other components of current meningococcal vaccines. Reactivity of the bactericidal hmAbs was confirmed to a single ca. 35 kDa protein in western blots. Unequivocal identification of this antigen is currently ongoing. Collectively, our results provide proof-of-principle for the use of reverse vaccinology 2.0 as a powerful tool in the search for alternative meningococcal vaccine candidate antigens.https://www.frontiersin.org/article/10.3389/fimmu.2018.01621/fullNeisseria meningitidisinvasive meningococcal diseasereverse vaccinology 2.0human monoclonal antibodiesvaccines |
| spellingShingle | Fadil A. Bidmos Simon Nadel Simon Nadel Gavin R. Screaton J. Simon Kroll Paul R. Langford Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0 Frontiers in Immunology Neisseria meningitidis invasive meningococcal disease reverse vaccinology 2.0 human monoclonal antibodies vaccines |
| title | Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0 |
| title_full | Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0 |
| title_fullStr | Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0 |
| title_full_unstemmed | Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0 |
| title_short | Cross-Reactive Bactericidal Antimeningococcal Antibodies Can Be Isolated From Convalescing Invasive Meningococcal Disease Patients Using Reverse Vaccinology 2.0 |
| title_sort | cross reactive bactericidal antimeningococcal antibodies can be isolated from convalescing invasive meningococcal disease patients using reverse vaccinology 2 0 |
| topic | Neisseria meningitidis invasive meningococcal disease reverse vaccinology 2.0 human monoclonal antibodies vaccines |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01621/full |
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