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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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