Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish

Abstract Vaccination is critical for the future of aquaculture, and nucleic acid vaccines have a major potential for fighting emerging fish infectious diseases, yet their mechanisms remain poorly understood. We compared B-cell responses induced by an mRNA, a DNA, and an attenuated vaccine, all encod...

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Main Authors: Dean Porter, Catherine Collins, Andrea Mazzolini, Luc Jouneau, Vanessa Mhanna, Céline Coiffier, Mathilde Peruzzi, Yan Jaszczyszyn, Encarnita Mariotti-Ferrandiz, Francois Huetz, Bertrand Collet, Thierry Mora, Aleksandra M. Walczak, Bernard Verrier, Pierre Boudinot
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-025-01232-8
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author Dean Porter
Catherine Collins
Andrea Mazzolini
Luc Jouneau
Vanessa Mhanna
Céline Coiffier
Mathilde Peruzzi
Yan Jaszczyszyn
Encarnita Mariotti-Ferrandiz
Francois Huetz
Bertrand Collet
Thierry Mora
Aleksandra M. Walczak
Bernard Verrier
Pierre Boudinot
author_facet Dean Porter
Catherine Collins
Andrea Mazzolini
Luc Jouneau
Vanessa Mhanna
Céline Coiffier
Mathilde Peruzzi
Yan Jaszczyszyn
Encarnita Mariotti-Ferrandiz
Francois Huetz
Bertrand Collet
Thierry Mora
Aleksandra M. Walczak
Bernard Verrier
Pierre Boudinot
author_sort Dean Porter
collection DOAJ
description Abstract Vaccination is critical for the future of aquaculture, and nucleic acid vaccines have a major potential for fighting emerging fish infectious diseases, yet their mechanisms remain poorly understood. We compared B-cell responses induced by an mRNA, a DNA, and an attenuated vaccine, all encoding the same antigen against a fish rhabdovirus. Rainbow trout IgHμ repertoires were examined to investigate how vaccines reshape clonal composition and complexity of the B-cell repertoire. The attenuated virus drove protection through a small number of highly shared public clonotypes encoding neutralizing antibodies. The mRNA vaccine profoundly remodelled the repertoire in some individuals and induces low, but still protective, neutralising Ab titers without public expansions. The DNA vaccine induced high neutralizing Ab titers, providing full protection with minimal impact on B-cell repertoire. Clustering analysis revealed partial sharing of private responses between fish. These findings highlight profound divergences between fish B-cell responses to nucleic acid and attenuated vaccines whilst all of three vaccines induce protective responses.
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issn 2059-0105
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publisher Nature Portfolio
record_format Article
series npj Vaccines
spelling doaj-art-ece3493df4fd4f608959dcbbbe4896ed2025-08-20T03:45:40ZengNature Portfolionpj Vaccines2059-01052025-07-0110111610.1038/s41541-025-01232-8Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fishDean Porter0Catherine Collins1Andrea Mazzolini2Luc Jouneau3Vanessa Mhanna4Céline Coiffier5Mathilde Peruzzi6Yan Jaszczyszyn7Encarnita Mariotti-Ferrandiz8Francois Huetz9Bertrand Collet10Thierry Mora11Aleksandra M. Walczak12Bernard Verrier13Pierre Boudinot14Université Paris-Saclay, INRAE, UVSQ, VIMUniversité Paris-Saclay, INRAE, UVSQ, VIMLaboratoire de physique de l’école normale supérieure (PSL University), CNRS, Sorbonne Université and Université Paris CitéUniversité Paris-Saclay, INRAE, UVSQ, VIMSorbonne Université, INSERM, Immunology-Immunopathology-Immunotherapy (i3)UMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie ThérapeutiqueUniversité Paris-Saclay, INRAE, UVSQ, VIMUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Sorbonne Université, INSERM, Immunology-Immunopathology-Immunotherapy (i3)Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and PathologyUniversité Paris-Saclay, INRAE, UVSQ, VIMLaboratoire de physique de l’école normale supérieure (PSL University), CNRS, Sorbonne Université and Université Paris CitéLaboratoire de physique de l’école normale supérieure (PSL University), CNRS, Sorbonne Université and Université Paris CitéUMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie ThérapeutiqueUniversité Paris-Saclay, INRAE, UVSQ, VIMAbstract Vaccination is critical for the future of aquaculture, and nucleic acid vaccines have a major potential for fighting emerging fish infectious diseases, yet their mechanisms remain poorly understood. We compared B-cell responses induced by an mRNA, a DNA, and an attenuated vaccine, all encoding the same antigen against a fish rhabdovirus. Rainbow trout IgHμ repertoires were examined to investigate how vaccines reshape clonal composition and complexity of the B-cell repertoire. The attenuated virus drove protection through a small number of highly shared public clonotypes encoding neutralizing antibodies. The mRNA vaccine profoundly remodelled the repertoire in some individuals and induces low, but still protective, neutralising Ab titers without public expansions. The DNA vaccine induced high neutralizing Ab titers, providing full protection with minimal impact on B-cell repertoire. Clustering analysis revealed partial sharing of private responses between fish. These findings highlight profound divergences between fish B-cell responses to nucleic acid and attenuated vaccines whilst all of three vaccines induce protective responses.https://doi.org/10.1038/s41541-025-01232-8
spellingShingle Dean Porter
Catherine Collins
Andrea Mazzolini
Luc Jouneau
Vanessa Mhanna
Céline Coiffier
Mathilde Peruzzi
Yan Jaszczyszyn
Encarnita Mariotti-Ferrandiz
Francois Huetz
Bertrand Collet
Thierry Mora
Aleksandra M. Walczak
Bernard Verrier
Pierre Boudinot
Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish
npj Vaccines
title Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish
title_full Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish
title_fullStr Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish
title_full_unstemmed Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish
title_short Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish
title_sort divergent b cell repertoire remodelling by mrna dna and live attenuated vaccines in fish
url https://doi.org/10.1038/s41541-025-01232-8
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