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Volume 15
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Article

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

by
Altan Yavuz
1,*,
Céline Coiffier
1,
Cynthia Garapon
1,
Serra Gurcan
2,
Claire Monge
1,
Jean-Yves Exposito
1,
Danielle Campiol Arruda
1 and
Bernard Verrier
1,*
1
Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, UMR 5305, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, CEDEX 07, 69367 Lyon, France
2
Precision NanoSystems Inc., 655 West Kent Avenue North Unit 50, Vancouver, BC V6P 6T7, Canada
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2023, 15(3), 1009; https://doi.org/10.3390/pharmaceutics15031009
Submission received: 17 February 2023 / Revised: 13 March 2023 / Accepted: 18 March 2023 / Published: 21 March 2023
(This article belongs to the Special Issue State-of-Art in mRNA Therapeutics and Gene Delivery)
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Abstract

mRNA-based vaccines have made a leap forward since the SARS-CoV-2 pandemic and are currently used to develop anti-infectious therapies. If the selection of a delivery system and an optimized mRNA sequence are two key factors to reach in vivo efficacy, the optimal administration route for those vaccines remains unclear. We investigated the influence of lipid components and immunization route regarding the intensity and quality of humoral immune responses in mice. The immunogenicity of HIV-p55Gag encoded mRNA encapsulated into D-Lin-MC3-DMA or GenVoy-ionizable lipid-based LNPs was compared after intramuscular or subcutaneous routes. Three sequential mRNA vaccines were administrated followed by a heterologous boost composed of p24-HIV protein antigen. Despite equivalent IgG kinetic profiles of general humoral responses, IgG1/IgG2a ratio analysis showed a Th2/Th1 balance toward a Th1-biased cellular immune response when both LNPs were administrated via the intramuscular route. Surprisingly, a Th2-biased antibody immunity was observed when DLin-containing vaccine was injected subcutaneously. A protein-based vaccine boost appeared to reverse this balance to a cellular-biased response correlated to an increase in antibody avidity. Our finding suggests that the intrinsic adjuvant effect of ionizable lipids appears to be dependent on the delivery route used, which could be relevant to reach potent and long-lasting immunity after mRNA-based immunization.
Keywords: mRNA-vaccine; lipid nanoparticles; gag HIV-1; administration routes; heterologous protein boost; Th2/Th1 polarization mRNA-vaccine; lipid nanoparticles; gag HIV-1; administration routes; heterologous protein boost; Th2/Th1 polarization

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MDPI and ACS Style

Yavuz, A.; Coiffier, C.; Garapon, C.; Gurcan, S.; Monge, C.; Exposito, J.-Y.; Arruda, D.C.; Verrier, B. DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice. Pharmaceutics 2023, 15, 1009. https://doi.org/10.3390/pharmaceutics15031009

AMA Style

Yavuz A, Coiffier C, Garapon C, Gurcan S, Monge C, Exposito J-Y, Arruda DC, Verrier B. DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice. Pharmaceutics. 2023; 15(3):1009. https://doi.org/10.3390/pharmaceutics15031009

Chicago/Turabian Style

Yavuz, Altan, Céline Coiffier, Cynthia Garapon, Serra Gurcan, Claire Monge, Jean-Yves Exposito, Danielle Campiol Arruda, and Bernard Verrier. 2023. "DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice" Pharmaceutics 15, no. 3: 1009. https://doi.org/10.3390/pharmaceutics15031009

APA Style

Yavuz, A., Coiffier, C., Garapon, C., Gurcan, S., Monge, C., Exposito, J.-Y., Arruda, D. C., & Verrier, B. (2023). DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice. Pharmaceutics, 15(3), 1009. https://doi.org/10.3390/pharmaceutics15031009

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