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Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models
Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen p...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477636/ https://www.ncbi.nlm.nih.gov/pubmed/34594333 http://dx.doi.org/10.3389/fimmu.2021.719315 |
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author | Micoli, Francesca Alfini, Renzo Di Benedetto, Roberta Necchi, Francesca Schiavo, Fabiola Mancini, Francesca Carducci, Martina Oldrini, Davide Pitirollo, Olimpia Gasperini, Gianmarco Balocchi, Cristiana Bechi, Nicoletta Brunelli, Brunella Piccioli, Diego Adamo, Roberto |
author_facet | Micoli, Francesca Alfini, Renzo Di Benedetto, Roberta Necchi, Francesca Schiavo, Fabiola Mancini, Francesca Carducci, Martina Oldrini, Davide Pitirollo, Olimpia Gasperini, Gianmarco Balocchi, Cristiana Bechi, Nicoletta Brunelli, Brunella Piccioli, Diego Adamo, Roberto |
author_sort | Micoli, Francesca |
collection | PubMed |
description | Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides. Here, we investigated the impact of saccharide length, density, and attachment site on the immune response elicited by GMMA in animal models, using a variety of structurally diverse polysaccharides from different pathogens (i.e., Neisseria meningitidis serogroup A and C, Haemophilus influenzae type b, and streptococcus Group A Carbohydrate and Salmonella Typhi Vi). Anti-polysaccharide immune response was not affected by the number of saccharides per GMMA particle. However, lower saccharide loading can better preserve the immunogenicity of GMMA as antigen. In contrast, saccharide length needs to be optimized for each specific antigen. Interestingly, GMMA conjugates induced strong functional immune response even when the polysaccharides were linked to sugars on GMMA. We also verified that GMMA conjugates elicit a T-dependent humoral immune response to polysaccharides that is strictly dependent on the nature of the polysaccharide. The results obtained are important to design novel glycoconjugate vaccines using GMMA as carrier and support the development of multicomponent glycoconjugate vaccines where GMMA can play the dual role of carrier and antigen. In addition, this work provides significant insights into the mechanism of action of glycoconjugates. |
format | Online Article Text |
id | pubmed-8477636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84776362021-09-29 Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models Micoli, Francesca Alfini, Renzo Di Benedetto, Roberta Necchi, Francesca Schiavo, Fabiola Mancini, Francesca Carducci, Martina Oldrini, Davide Pitirollo, Olimpia Gasperini, Gianmarco Balocchi, Cristiana Bechi, Nicoletta Brunelli, Brunella Piccioli, Diego Adamo, Roberto Front Immunol Immunology Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides. Here, we investigated the impact of saccharide length, density, and attachment site on the immune response elicited by GMMA in animal models, using a variety of structurally diverse polysaccharides from different pathogens (i.e., Neisseria meningitidis serogroup A and C, Haemophilus influenzae type b, and streptococcus Group A Carbohydrate and Salmonella Typhi Vi). Anti-polysaccharide immune response was not affected by the number of saccharides per GMMA particle. However, lower saccharide loading can better preserve the immunogenicity of GMMA as antigen. In contrast, saccharide length needs to be optimized for each specific antigen. Interestingly, GMMA conjugates induced strong functional immune response even when the polysaccharides were linked to sugars on GMMA. We also verified that GMMA conjugates elicit a T-dependent humoral immune response to polysaccharides that is strictly dependent on the nature of the polysaccharide. The results obtained are important to design novel glycoconjugate vaccines using GMMA as carrier and support the development of multicomponent glycoconjugate vaccines where GMMA can play the dual role of carrier and antigen. In addition, this work provides significant insights into the mechanism of action of glycoconjugates. Frontiers Media S.A. 2021-09-14 /pmc/articles/PMC8477636/ /pubmed/34594333 http://dx.doi.org/10.3389/fimmu.2021.719315 Text en Copyright © 2021 Micoli, Alfini, Di Benedetto, Necchi, Schiavo, Mancini, Carducci, Oldrini, Pitirollo, Gasperini, Balocchi, Bechi, Brunelli, Piccioli and Adamo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Micoli, Francesca Alfini, Renzo Di Benedetto, Roberta Necchi, Francesca Schiavo, Fabiola Mancini, Francesca Carducci, Martina Oldrini, Davide Pitirollo, Olimpia Gasperini, Gianmarco Balocchi, Cristiana Bechi, Nicoletta Brunelli, Brunella Piccioli, Diego Adamo, Roberto Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models |
title | Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models |
title_full | Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models |
title_fullStr | Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models |
title_full_unstemmed | Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models |
title_short | Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models |
title_sort | generalized modules for membrane antigens as carrier for polysaccharides: impact of sugar length, density, and attachment site on the immune response elicited in animal models |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477636/ https://www.ncbi.nlm.nih.gov/pubmed/34594333 http://dx.doi.org/10.3389/fimmu.2021.719315 |
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