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Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.


ABSTRACT: Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.

SUBMITTER: Alameh MG 

PROVIDER: S-EPMC8566475 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.

Alameh Mohamad-Gabriel MG   Tombácz István I   Bettini Emily E   Lederer Katlyn K   Sittplangkoon Chutamath C   Wilmore Joel R JR   Gaudette Brian T BT   Soliman Ousamah Y OY   Pine Matthew M   Hicks Philip P   Manzoni Tomaz B TB   Knox James J JJ   Johnson John L JL   Laczkó Dorottya D   Muramatsu Hiromi H   Davis Benjamin B   Meng Wenzhao W   Rosenfeld Aaron M AM   Strohmeier Shirin S   Lin Paulo J C PJC   Mui Barbara L BL   Tam Ying K YK   Karikó Katalin K   Jacquet Alain A   Krammer Florian F   Bates Paul P   Cancro Michael P MP   Weissman Drew D   Luning Prak Eline T ET   Allman David D   Locci Michela M   Pardi Norbert N  

Immunity 20211104 12


Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity  ...[more]

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