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Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA

Generalized Modules for Membrane Antigens (GMMA) are outer membrane exosomes purified from Gram-negative bacteria genetically mutated to increase blebbing and reduce risk of reactogenicity. This is commonly achieved through modification of the lipid A portion of lipopolysaccharide. GMMA faithfully r...

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Autores principales: Tondi, Serena, Clemente, Bruna, Esposito, Carmen, Sammicheli, Chiara, Tavarini, Simona, Martin, Laura B., Rossi, Omar, Micoli, Francesca, Bartolini, Erika, Brazzoli, Michela, Ulivieri, Cristina, Blohmke, Christoph J., Schiavetti, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851470/
https://www.ncbi.nlm.nih.gov/pubmed/35186786
http://dx.doi.org/10.3389/fcimb.2022.767153
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author Tondi, Serena
Clemente, Bruna
Esposito, Carmen
Sammicheli, Chiara
Tavarini, Simona
Martin, Laura B.
Rossi, Omar
Micoli, Francesca
Bartolini, Erika
Brazzoli, Michela
Ulivieri, Cristina
Blohmke, Christoph J.
Schiavetti, Francesca
author_facet Tondi, Serena
Clemente, Bruna
Esposito, Carmen
Sammicheli, Chiara
Tavarini, Simona
Martin, Laura B.
Rossi, Omar
Micoli, Francesca
Bartolini, Erika
Brazzoli, Michela
Ulivieri, Cristina
Blohmke, Christoph J.
Schiavetti, Francesca
author_sort Tondi, Serena
collection PubMed
description Generalized Modules for Membrane Antigens (GMMA) are outer membrane exosomes purified from Gram-negative bacteria genetically mutated to increase blebbing and reduce risk of reactogenicity. This is commonly achieved through modification of the lipid A portion of lipopolysaccharide. GMMA faithfully resemble the bacterial outer membrane surface, and therefore represent a powerful and flexible platform for vaccine development. Although GMMA-based vaccines have been demonstrated to induce a strong and functional antibody response in animals and humans maintaining an acceptable reactogenicity profile, the overall impact on immune cells and their mode of action are still poorly understood. To characterize the GMMA-induced immune response, we stimulated human peripheral blood mononuclear cells (hPBMCs) with GMMA from Shigella sonnei. We studied GMMA both with wild-type hexa-acylated lipid A and with the corresponding less reactogenic penta-acylated form. Using multicolor flow cytometry, we assessed the activation of immune cell subsets and we profiled intracellular cytokine production after GMMA stimulation. Moreover, we measured the secretion of thirty cytokines/chemokines in the cell culture supernatants. Our data indicated activation of monocytes, dendritic, NK, B, and γδ T cells. Comparison of the cytokine responses showed that, although the two GMMA have qualitatively similar profiles, GMMA with modified penta-acylated lipid A induced a lower production of pro-inflammatory cytokines/chemokines compared to GMMA with wild-type lipid A. Intracellular cytokine staining indicated monocytes and dendritic cells as the main source of the cytokines produced. Overall, these data provide new insights into the activation of key immune cells potentially targeted by GMMA-based vaccines.
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spelling pubmed-88514702022-02-18 Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA Tondi, Serena Clemente, Bruna Esposito, Carmen Sammicheli, Chiara Tavarini, Simona Martin, Laura B. Rossi, Omar Micoli, Francesca Bartolini, Erika Brazzoli, Michela Ulivieri, Cristina Blohmke, Christoph J. Schiavetti, Francesca Front Cell Infect Microbiol Cellular and Infection Microbiology Generalized Modules for Membrane Antigens (GMMA) are outer membrane exosomes purified from Gram-negative bacteria genetically mutated to increase blebbing and reduce risk of reactogenicity. This is commonly achieved through modification of the lipid A portion of lipopolysaccharide. GMMA faithfully resemble the bacterial outer membrane surface, and therefore represent a powerful and flexible platform for vaccine development. Although GMMA-based vaccines have been demonstrated to induce a strong and functional antibody response in animals and humans maintaining an acceptable reactogenicity profile, the overall impact on immune cells and their mode of action are still poorly understood. To characterize the GMMA-induced immune response, we stimulated human peripheral blood mononuclear cells (hPBMCs) with GMMA from Shigella sonnei. We studied GMMA both with wild-type hexa-acylated lipid A and with the corresponding less reactogenic penta-acylated form. Using multicolor flow cytometry, we assessed the activation of immune cell subsets and we profiled intracellular cytokine production after GMMA stimulation. Moreover, we measured the secretion of thirty cytokines/chemokines in the cell culture supernatants. Our data indicated activation of monocytes, dendritic, NK, B, and γδ T cells. Comparison of the cytokine responses showed that, although the two GMMA have qualitatively similar profiles, GMMA with modified penta-acylated lipid A induced a lower production of pro-inflammatory cytokines/chemokines compared to GMMA with wild-type lipid A. Intracellular cytokine staining indicated monocytes and dendritic cells as the main source of the cytokines produced. Overall, these data provide new insights into the activation of key immune cells potentially targeted by GMMA-based vaccines. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8851470/ /pubmed/35186786 http://dx.doi.org/10.3389/fcimb.2022.767153 Text en Copyright © 2022 Tondi, Clemente, Esposito, Sammicheli, Tavarini, Martin, Rossi, Micoli, Bartolini, Brazzoli, Ulivieri, Blohmke and Schiavetti 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 Cellular and Infection Microbiology
Tondi, Serena
Clemente, Bruna
Esposito, Carmen
Sammicheli, Chiara
Tavarini, Simona
Martin, Laura B.
Rossi, Omar
Micoli, Francesca
Bartolini, Erika
Brazzoli, Michela
Ulivieri, Cristina
Blohmke, Christoph J.
Schiavetti, Francesca
Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA
title Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA
title_full Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA
title_fullStr Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA
title_full_unstemmed Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA
title_short Dissecting in Vitro the Activation of Human Immune Response Induced by Shigella sonnei GMMA
title_sort dissecting in vitro the activation of human immune response induced by shigella sonnei gmma
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851470/
https://www.ncbi.nlm.nih.gov/pubmed/35186786
http://dx.doi.org/10.3389/fcimb.2022.767153
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