In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway
IntroductionSeveral diseases caused by the dysregulation of complement activation can be treated with inhibitors of the complement components C5 and/or C3. However, complement is required for serum bactericidal activity (SBA) against encapsulated Gram-negative bacteria. Therefore, C3 and C5 inhibiti...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1180833/full |
| _version_ | 1797791893274230784 |
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| author | Emma Ispasanie Emma Ispasanie Lukas Muri Lukas Muri Marc Schmid Marc Schmid Anna Schubart Christine Thorburn Natasa Zamurovic Thomas Holbro Michael Kammüller Gerd Pluschke Gerd Pluschke |
| author_facet | Emma Ispasanie Emma Ispasanie Lukas Muri Lukas Muri Marc Schmid Marc Schmid Anna Schubart Christine Thorburn Natasa Zamurovic Thomas Holbro Michael Kammüller Gerd Pluschke Gerd Pluschke |
| author_sort | Emma Ispasanie |
| collection | DOAJ |
| description | IntroductionSeveral diseases caused by the dysregulation of complement activation can be treated with inhibitors of the complement components C5 and/or C3. However, complement is required for serum bactericidal activity (SBA) against encapsulated Gram-negative bacteria. Therefore, C3 and C5 inhibition increases the risk of invasive disease, in particular by Neisseria meningitidis. As inhibitors against complement components other than C3 and C5 may carry a reduced risk of infection, we compared the effect of inhibitors targeting the terminal pathway (C5), the central complement component C3, the alternative pathway (FB and FD), and the lectin pathway (MASP-2) on SBA against serogroup B meningococci.MethodsSerum from adults was collected before and after vaccination with the meningococcal serogroup B vaccine 4CMenB and tested for meningococcal killing. Since the B capsular polysaccharide is structurally similar to certain human polysaccharides, 4CMenB was designed to elicit antibodies against meningococcal outer membrane proteins.ResultsWhile only a few pre-vaccination sera showed SBA against the tested B meningococcal isolates, 4CMenB vaccination induced potent complement-activating IgG titers against isolates expressing a matching allele of the bacterial cell surface-exposed factor H-binding protein (fHbp). SBA triggered by these cell surface protein-specific antibodies was blocked by C5 and reduced by C3 inhibition, whereas alternative (factor B and D) and lectin (MASP-2) pathway inhibitors had no effect on the SBA of post-4CMenB vaccination sera.DiscussionCompared to the SBA triggered by A,C,W,Y capsule polysaccharide conjugate vaccination, SBA against B meningococci expressing a matching fHbp allele was remarkably resilient against the alternative pathway inhibition. |
| first_indexed | 2024-03-13T02:26:14Z |
| format | Article |
| id | doaj.art-98f0748c5c004296ac5b23564869901e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T02:26:14Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-98f0748c5c004296ac5b23564869901e2023-06-30T02:56:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11808331180833In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathwayEmma Ispasanie0Emma Ispasanie1Lukas Muri2Lukas Muri3Marc Schmid4Marc Schmid5Anna Schubart6Christine Thorburn7Natasa Zamurovic8Thomas Holbro9Michael Kammüller10Gerd Pluschke11Gerd Pluschke12Swiss Tropical and Public Health Institute, Molecular Immunology Unit, Basel, SwitzerlandUniversity of Basel, Basel, SwitzerlandSwiss Tropical and Public Health Institute, Molecular Immunology Unit, Basel, SwitzerlandUniversity of Basel, Basel, SwitzerlandSwiss Tropical and Public Health Institute, Molecular Immunology Unit, Basel, SwitzerlandUniversity of Basel, Basel, SwitzerlandNovartis Institutes for Biomedical Research, Department Autoimmunity, Transplantation and Inflammation, Basel, SwitzerlandNovartis Pharma AG, London, United KingdomNovartis Institutes for Biomedical Research, Translational Medicine-Preclinical Safety, Basel, SwitzerlandGlobal Drug Development, Novartis Pharma AG, Basel, SwitzerlandNovartis Institutes for Biomedical Research, Translational Medicine-Preclinical Safety, Basel, SwitzerlandSwiss Tropical and Public Health Institute, Molecular Immunology Unit, Basel, SwitzerlandUniversity of Basel, Basel, SwitzerlandIntroductionSeveral diseases caused by the dysregulation of complement activation can be treated with inhibitors of the complement components C5 and/or C3. However, complement is required for serum bactericidal activity (SBA) against encapsulated Gram-negative bacteria. Therefore, C3 and C5 inhibition increases the risk of invasive disease, in particular by Neisseria meningitidis. As inhibitors against complement components other than C3 and C5 may carry a reduced risk of infection, we compared the effect of inhibitors targeting the terminal pathway (C5), the central complement component C3, the alternative pathway (FB and FD), and the lectin pathway (MASP-2) on SBA against serogroup B meningococci.MethodsSerum from adults was collected before and after vaccination with the meningococcal serogroup B vaccine 4CMenB and tested for meningococcal killing. Since the B capsular polysaccharide is structurally similar to certain human polysaccharides, 4CMenB was designed to elicit antibodies against meningococcal outer membrane proteins.ResultsWhile only a few pre-vaccination sera showed SBA against the tested B meningococcal isolates, 4CMenB vaccination induced potent complement-activating IgG titers against isolates expressing a matching allele of the bacterial cell surface-exposed factor H-binding protein (fHbp). SBA triggered by these cell surface protein-specific antibodies was blocked by C5 and reduced by C3 inhibition, whereas alternative (factor B and D) and lectin (MASP-2) pathway inhibitors had no effect on the SBA of post-4CMenB vaccination sera.DiscussionCompared to the SBA triggered by A,C,W,Y capsule polysaccharide conjugate vaccination, SBA against B meningococci expressing a matching fHbp allele was remarkably resilient against the alternative pathway inhibition.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1180833/fullNeisseria meningitidisserum bactericidal activitycomplement inhibitorsserogroup B vaccinealternative pathwayimmunotherapy |
| spellingShingle | Emma Ispasanie Emma Ispasanie Lukas Muri Lukas Muri Marc Schmid Marc Schmid Anna Schubart Christine Thorburn Natasa Zamurovic Thomas Holbro Michael Kammüller Gerd Pluschke Gerd Pluschke In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway Frontiers in Immunology Neisseria meningitidis serum bactericidal activity complement inhibitors serogroup B vaccine alternative pathway immunotherapy |
| title | In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway |
| title_full | In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway |
| title_fullStr | In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway |
| title_full_unstemmed | In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway |
| title_short | In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway |
| title_sort | in vaccinated individuals serum bactericidal activity against b meningococci is abrogated by c5 inhibition but not by inhibition of the alternative complement pathway |
| topic | Neisseria meningitidis serum bactericidal activity complement inhibitors serogroup B vaccine alternative pathway immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1180833/full |
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