Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study
Shigella is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against Shigella species are currently under...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.971866/full |
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| author | Melissa C. Kapulu Melissa C. Kapulu Usman Nakakana Antonella S. Sciré Eleanna Sarakinou Valentino Conti Omar Rossi Alessandra Acquaviva Francesca Necchi Christina W. Obiero Laura B. Martin Philip Bejon Philip Bejon Patricia Njuguna Francesca Micoli Audino Podda |
| author_facet | Melissa C. Kapulu Melissa C. Kapulu Usman Nakakana Antonella S. Sciré Eleanna Sarakinou Valentino Conti Omar Rossi Alessandra Acquaviva Francesca Necchi Christina W. Obiero Laura B. Martin Philip Bejon Philip Bejon Patricia Njuguna Francesca Micoli Audino Podda |
| author_sort | Melissa C. Kapulu |
| collection | DOAJ |
| description | Shigella is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against Shigella species are currently under clinical development. The investigational 1790GAHB vaccine against Shigella sonnei is based on GMMA (Generalized Modules for Membrane Antigens) technology. The vaccine was well tolerated and induced high antibody levels in early-phase clinical trials in both Shigella-endemic and non-endemic settings. The present analysis assessed the bactericidal activity of antibodies induced by 1790GAHB in healthy Kenyan adults during a phase 2a, controlled, randomized study (NCT02676895). Participants received two doses of 1790GAHB 4 weeks apart containing either 1.5/25 µg or 6/100 µg O antigen/protein, or active comparator vaccines (Control). Serum bactericidal activity (SBA) against S. sonnei was assessed at pre-vaccination (D1), 28 days post-first dose (D29) and 28 days post-second dose (D57), using a luminescence-based assay. Most participants had SBA titers above the lower limit of quantification of the assay at D1. SBA geometric mean titers increased 3.4-fold in the 1.5/25 µg group and 6.3-fold in the 6/100 µg group by D29 and were maintained at D57. There was no increase in SBA geometric mean titers in the Control group. A strong correlation was observed between SBA titers and anti-S. sonnei lipopolysaccharide serum immunoglobulin G antibody concentrations (Pearson correlation coefficient = 0.918), indicating that SBA can effectively complement enzyme-linked immunosorbent assay data by indicating the functionality of 1790GAHB-induced antibodies. |
| first_indexed | 2024-04-11T09:51:16Z |
| format | Article |
| id | doaj.art-e4da192802074f8ebb9eb4be6d034a3a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T09:51:16Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-e4da192802074f8ebb9eb4be6d034a3a2022-12-22T04:30:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.971866971866Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized studyMelissa C. Kapulu0Melissa C. Kapulu1Usman Nakakana2Antonella S. Sciré3Eleanna Sarakinou4Valentino Conti5Omar Rossi6Alessandra Acquaviva7Francesca Necchi8Christina W. Obiero9Laura B. Martin10Philip Bejon11Philip Bejon12Patricia Njuguna13Francesca Micoli14Audino Podda15Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, KenyaCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyClinical Research Department, KEMRI-Wellcome Trust Programme, Kilifi, KenyaGSK Vaccines Institute for Global Health, Siena, ItalyKenya Medical Research Institute (KEMRI)-Wellcome Trust Programme, Kilifi, KenyaCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomClinical Research Department, KEMRI-Wellcome Trust Programme, Kilifi, KenyaGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyShigella is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against Shigella species are currently under clinical development. The investigational 1790GAHB vaccine against Shigella sonnei is based on GMMA (Generalized Modules for Membrane Antigens) technology. The vaccine was well tolerated and induced high antibody levels in early-phase clinical trials in both Shigella-endemic and non-endemic settings. The present analysis assessed the bactericidal activity of antibodies induced by 1790GAHB in healthy Kenyan adults during a phase 2a, controlled, randomized study (NCT02676895). Participants received two doses of 1790GAHB 4 weeks apart containing either 1.5/25 µg or 6/100 µg O antigen/protein, or active comparator vaccines (Control). Serum bactericidal activity (SBA) against S. sonnei was assessed at pre-vaccination (D1), 28 days post-first dose (D29) and 28 days post-second dose (D57), using a luminescence-based assay. Most participants had SBA titers above the lower limit of quantification of the assay at D1. SBA geometric mean titers increased 3.4-fold in the 1.5/25 µg group and 6.3-fold in the 6/100 µg group by D29 and were maintained at D57. There was no increase in SBA geometric mean titers in the Control group. A strong correlation was observed between SBA titers and anti-S. sonnei lipopolysaccharide serum immunoglobulin G antibody concentrations (Pearson correlation coefficient = 0.918), indicating that SBA can effectively complement enzyme-linked immunosorbent assay data by indicating the functionality of 1790GAHB-induced antibodies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.971866/fullshigella sonneigeneralized modules for membrane antigens (GMMA)1790GAHB vaccinefunctional antibodyserum bactericidal activityIgG |
| spellingShingle | Melissa C. Kapulu Melissa C. Kapulu Usman Nakakana Antonella S. Sciré Eleanna Sarakinou Valentino Conti Omar Rossi Alessandra Acquaviva Francesca Necchi Christina W. Obiero Laura B. Martin Philip Bejon Philip Bejon Patricia Njuguna Francesca Micoli Audino Podda Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study Frontiers in Immunology shigella sonnei generalized modules for membrane antigens (GMMA) 1790GAHB vaccine functional antibody serum bactericidal activity IgG |
| title | Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study |
| title_full | Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study |
| title_fullStr | Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study |
| title_full_unstemmed | Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study |
| title_short | Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study |
| title_sort | complement mediated serum bactericidal activity of antibodies elicited by the shigella sonnei gmma vaccine in adults from a shigellosis endemic country exploratory analysis of a phase 2a randomized study |
| topic | shigella sonnei generalized modules for membrane antigens (GMMA) 1790GAHB vaccine functional antibody serum bactericidal activity IgG |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.971866/full |
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