Distinct dynamics of mRNA LNPs in mice and nonhuman primates revealed by in vivo imaging.


Journal

NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863

Informations de publication

Date de publication:
20 Jun 2024
Historique:
received: 07 12 2023
accepted: 03 06 2024
medline: 21 6 2024
pubmed: 21 6 2024
entrez: 20 6 2024
Statut: epublish

Résumé

The characterization of vaccine distribution to relevant tissues after in vivo administration is critical to understanding their mechanisms of action. Vaccines based on mRNA lipid nanoparticles (LNPs) are now being widely considered against infectious diseases and cancer. Here, we used in vivo imaging approaches to compare the trafficking of two LNP formulations encapsulating mRNA following intramuscular administration: DLin-MC3-DMA (MC3) and the recently developed DOG-IM4. The mRNA formulated in DOG-IM4 LNPs persisted at the injection site, whereas mRNA formulated in MC3 LNPs rapidly migrated to the draining lymph nodes. Furthermore, MC3 LNPs induced the fastest increase in blood neutrophil counts after injection and greater inflammation, as shown by IL-1RA, IL-15, CCL-1, and IL-6 concentrations in nonhuman primate sera. These observations highlight the influence of the nature of the LNP on mRNA vaccine distribution and early immune responses.

Identifiants

pubmed: 38902327
doi: 10.1038/s41541-024-00900-5
pii: 10.1038/s41541-024-00900-5
doi:

Types de publication

Journal Article

Langues

eng

Pagination

113

Informations de copyright

© 2024. The Author(s).

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Auteurs

Katia Lemdani (K)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.
Sanofi, Marcy-L'étoile, France.

Romain Marlin (R)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Céline Mayet (C)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Vladimir Perkov (V)

Sanofi, Marcy-L'étoile, France.

Quentin Pascal (Q)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Manon Ripoll (M)

Sanofi, Marcy-L'étoile, France.

Francis Relouzat (F)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Nina Dhooge (N)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Laetitia Bossevot (L)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Nathalie Dereuddre-Bosquet (N)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Gihad Dargazanli (G)

Integrated Drug Discovery, Sanofi, Chilly-Mazarin, France.

Kevin Thibaut-Duprey (K)

Sanofi, Marcy-L'étoile, France.

Jean Haensler (J)

Sanofi, Marcy-L'étoile, France.

Catherine Chapon (C)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Christine Prost (C)

Sanofi, Marcy-L'étoile, France. christine.prost@sanofi.com.

Roger Le Grand (R)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France. roger.le-grand@cea.fr.

Classifications MeSH