Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/47279 |
Resumo: | Copyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). |
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Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharideNeisseria meningitidisCarbohydratesStructural glycobiologyVaccinesCopyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).Meningococcal meningitis remains a substantial cause of mortality and morbidity worldwide. Until recently, countries in the African meningitis belt were susceptible to devastating outbreaks, largely attributed to serogroup A Neisseria meningitidis (MenA). Vaccination with glycoconjugates of MenA capsular polysaccharide led to an almost complete elimination of MenA clinical cases. To understand the molecular basis of vaccine-induced protection, we generated a panel of oligosaccharide fragments of different lengths and tested them with polyclonal and monoclonal antibodies by inhibition enzyme-linked immunosorbent assay, surface plasmon resonance, and competitive human serum bactericidal assay, which is a surrogate for protection. The epitope was shown to optimize between three and six repeating units and to be O-acetylated. The molecular interactions between a protective monoclonal antibody and a MenA capsular polysaccharide fragment were further elucidated at the atomic level by saturation transfer difference NMR spectroscopy and X-ray crystallography. The epitope consists of a trisaccharide anchored to the antibody via the O- and N-acetyl moieties through either H-bonding or CH–π interactions. In silico docking showed that 3-O-acetylation of the upstream residue is essential for antibody binding, while O-acetate could be equally accommodated at three and four positions of the other two residues. These results shed light on the mechanism of action of current MenA vaccines and provide a foundation for the rational design of improved therapies.This work was sponsored by GlaxoSmithKline Biologicals and has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement 675671.National Academy of SciencesRepositório da Universidade de LisboaHenriques, PedroDello Iacono, LuciaGimeno, AnaBiolchi, AlessiaRomano, Maria RosariaArda, AnaBernardes, Gonçalo J. L.Jimenez-Barbero, JesusBerti, FrancescoRappuoli, RinoAdamo, Roberto2021-04-07T16:24:48Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47279engProc Natl Acad Sci U S A. 2020 Nov 24;117(47):29795-298020027-842410.1073/pnas.20113851171091-6490info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:50:06Zoai:repositorio.ul.pt:10451/47279Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:21.882867Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| title |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| spellingShingle |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide Henriques, Pedro Neisseria meningitidis Carbohydrates Structural glycobiology Vaccines |
| title_short |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| title_full |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| title_fullStr |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| title_full_unstemmed |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| title_sort |
Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide |
| author |
Henriques, Pedro |
| author_facet |
Henriques, Pedro Dello Iacono, Lucia Gimeno, Ana Biolchi, Alessia Romano, Maria Rosaria Arda, Ana Bernardes, Gonçalo J. L. Jimenez-Barbero, Jesus Berti, Francesco Rappuoli, Rino Adamo, Roberto |
| author_role |
author |
| author2 |
Dello Iacono, Lucia Gimeno, Ana Biolchi, Alessia Romano, Maria Rosaria Arda, Ana Bernardes, Gonçalo J. L. Jimenez-Barbero, Jesus Berti, Francesco Rappuoli, Rino Adamo, Roberto |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Henriques, Pedro Dello Iacono, Lucia Gimeno, Ana Biolchi, Alessia Romano, Maria Rosaria Arda, Ana Bernardes, Gonçalo J. L. Jimenez-Barbero, Jesus Berti, Francesco Rappuoli, Rino Adamo, Roberto |
| dc.subject.por.fl_str_mv |
Neisseria meningitidis Carbohydrates Structural glycobiology Vaccines |
| topic |
Neisseria meningitidis Carbohydrates Structural glycobiology Vaccines |
| description |
Copyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-04-07T16:24:48Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/47279 |
| url |
http://hdl.handle.net/10451/47279 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29795-29802 0027-8424 10.1073/pnas.2011385117 1091-6490 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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National Academy of Sciences |
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National Academy of Sciences |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134539203739648 |