Mimicking immune complexes for efficient antibody responses

Efficient antibody responses are crucial for combating infectious diseases and vaccination remains a cornerstone of this effort. This study introduces a novel approach for enhancing immune responses in wild-type mice by utilizing pre-formed immune complexes, using the receptor-binding domain (RBD) o...

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Main Authors: Jonathan Schönfelder, Omar El Ayoubi, Oles Havryliuk, Rüdiger Groß, Alina Seidel, Tamam Bakchoul, Jan Münch, Hassan Jumaa, Corinna S. Setz
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1570487/full
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author Jonathan Schönfelder
Omar El Ayoubi
Oles Havryliuk
Rüdiger Groß
Alina Seidel
Tamam Bakchoul
Jan Münch
Hassan Jumaa
Corinna S. Setz
author_facet Jonathan Schönfelder
Omar El Ayoubi
Oles Havryliuk
Rüdiger Groß
Alina Seidel
Tamam Bakchoul
Jan Münch
Hassan Jumaa
Corinna S. Setz
author_sort Jonathan Schönfelder
collection DOAJ
description Efficient antibody responses are crucial for combating infectious diseases and vaccination remains a cornerstone of this effort. This study introduces a novel approach for enhancing immune responses in wild-type mice by utilizing pre-formed immune complexes, using the receptor-binding domain (RBD) of SARS-CoV-2 as a model antigen to illustrate the broader potential of the concept. Specifically, we found that pre-treating the antigen with bis-maleimide, a chemical linker that facilitates protein cross-linking, significantly enhances antibody production. Moreover, in vitro cross-linking of antigen to unrelated IgG using bis-maleimide generated immune complexes that markedly enhanced antigen-specific antibody responses, likely by mimicking natural memory-like mechanisms, suggesting that bis-maleimide pre-treated antigens may similarly engage IgG in vivo. In contrast, antigen crosslinking with IgA or IgM did not yield comparable effects, highlighting the unique capacity of IgG to boost immunogenicity. By leveraging the principles of immune memory, this study demonstrates the potential of pre-formed immune complexes to significantly enhance vaccine efficacy using an antigen-independent strategy broadly applicable to diverse pathogens.
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publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-70d76052a0854f84bffdbd2377627f852025-08-20T02:20:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15704871570487Mimicking immune complexes for efficient antibody responsesJonathan Schönfelder0Omar El Ayoubi1Oles Havryliuk2Rüdiger Groß3Alina Seidel4Tamam Bakchoul5Jan Münch6Hassan Jumaa7Corinna S. Setz8Institute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm, GermanyCentre for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyInstitute of Immunology, Ulm University Medical Center, Ulm, GermanyEfficient antibody responses are crucial for combating infectious diseases and vaccination remains a cornerstone of this effort. This study introduces a novel approach for enhancing immune responses in wild-type mice by utilizing pre-formed immune complexes, using the receptor-binding domain (RBD) of SARS-CoV-2 as a model antigen to illustrate the broader potential of the concept. Specifically, we found that pre-treating the antigen with bis-maleimide, a chemical linker that facilitates protein cross-linking, significantly enhances antibody production. Moreover, in vitro cross-linking of antigen to unrelated IgG using bis-maleimide generated immune complexes that markedly enhanced antigen-specific antibody responses, likely by mimicking natural memory-like mechanisms, suggesting that bis-maleimide pre-treated antigens may similarly engage IgG in vivo. In contrast, antigen crosslinking with IgA or IgM did not yield comparable effects, highlighting the unique capacity of IgG to boost immunogenicity. By leveraging the principles of immune memory, this study demonstrates the potential of pre-formed immune complexes to significantly enhance vaccine efficacy using an antigen-independent strategy broadly applicable to diverse pathogens.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1570487/fullIgGB cellsantibody responsesadjuvantmemory
spellingShingle Jonathan Schönfelder
Omar El Ayoubi
Oles Havryliuk
Rüdiger Groß
Alina Seidel
Tamam Bakchoul
Jan Münch
Hassan Jumaa
Corinna S. Setz
Mimicking immune complexes for efficient antibody responses
Frontiers in Immunology
IgG
B cells
antibody responses
adjuvant
memory
title Mimicking immune complexes for efficient antibody responses
title_full Mimicking immune complexes for efficient antibody responses
title_fullStr Mimicking immune complexes for efficient antibody responses
title_full_unstemmed Mimicking immune complexes for efficient antibody responses
title_short Mimicking immune complexes for efficient antibody responses
title_sort mimicking immune complexes for efficient antibody responses
topic IgG
B cells
antibody responses
adjuvant
memory
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1570487/full
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