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Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production

Host antibody responses are pivotal for providing protection against infectious agents. We have pioneered a new class of self-assembling micelles based on pentablock copolymers that enhance antibody responses while providing a low inflammatory environment compared to traditional adjuvants. This type...

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Autores principales: Senapati, Sujata, Darling, Ross J., Ross, Kathleen A., Wannemeuhler, Michael J., Narasimhan, Balaji, Mallapragada, Surya K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336949/
https://www.ncbi.nlm.nih.gov/pubmed/34348905
http://dx.doi.org/10.1126/sciadv.abj1691
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author Senapati, Sujata
Darling, Ross J.
Ross, Kathleen A.
Wannemeuhler, Michael J.
Narasimhan, Balaji
Mallapragada, Surya K.
author_facet Senapati, Sujata
Darling, Ross J.
Ross, Kathleen A.
Wannemeuhler, Michael J.
Narasimhan, Balaji
Mallapragada, Surya K.
author_sort Senapati, Sujata
collection PubMed
description Host antibody responses are pivotal for providing protection against infectious agents. We have pioneered a new class of self-assembling micelles based on pentablock copolymers that enhance antibody responses while providing a low inflammatory environment compared to traditional adjuvants. This type of “just-right” immune response is critical in the rational design of vaccines for older adults. Here, we report on the mechanism of enhancement of antibody responses by pentablock copolymer micelles, which act as scaffolds for antigen presentation to B cells and cross-link B cell receptors, unlike other micelle-forming synthetic block copolymers. We exploited this unique mechanism and developed these scaffolds as a platform technology to produce antibodies in vitro. We show that this novel approach can be used to generate laboratory-scale quantities of therapeutic antibodies against multiple antigens, including those associated with SARS-CoV-2 and Yersinia pestis, further expanding the value of these nanomaterials to rapidly develop countermeasures against infectious diseases.
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spelling pubmed-83369492021-08-12 Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production Senapati, Sujata Darling, Ross J. Ross, Kathleen A. Wannemeuhler, Michael J. Narasimhan, Balaji Mallapragada, Surya K. Sci Adv Research Articles Host antibody responses are pivotal for providing protection against infectious agents. We have pioneered a new class of self-assembling micelles based on pentablock copolymers that enhance antibody responses while providing a low inflammatory environment compared to traditional adjuvants. This type of “just-right” immune response is critical in the rational design of vaccines for older adults. Here, we report on the mechanism of enhancement of antibody responses by pentablock copolymer micelles, which act as scaffolds for antigen presentation to B cells and cross-link B cell receptors, unlike other micelle-forming synthetic block copolymers. We exploited this unique mechanism and developed these scaffolds as a platform technology to produce antibodies in vitro. We show that this novel approach can be used to generate laboratory-scale quantities of therapeutic antibodies against multiple antigens, including those associated with SARS-CoV-2 and Yersinia pestis, further expanding the value of these nanomaterials to rapidly develop countermeasures against infectious diseases. American Association for the Advancement of Science 2021-08-04 /pmc/articles/PMC8336949/ /pubmed/34348905 http://dx.doi.org/10.1126/sciadv.abj1691 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Senapati, Sujata
Darling, Ross J.
Ross, Kathleen A.
Wannemeuhler, Michael J.
Narasimhan, Balaji
Mallapragada, Surya K.
Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production
title Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production
title_full Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production
title_fullStr Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production
title_full_unstemmed Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production
title_short Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production
title_sort self-assembling synthetic nanoadjuvant scaffolds cross-link b cell receptors and represent new platform technology for therapeutic antibody production
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336949/
https://www.ncbi.nlm.nih.gov/pubmed/34348905
http://dx.doi.org/10.1126/sciadv.abj1691
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