tetano
Editor, Senior Moderator
Immunity
. 2021 Nov 4;S1074-7613(21)00490-8.
doi: 10.1016/j.immuni.2021.11.001. Online ahead of print.
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Mohamad-Gabriel Alameh[SUP] 1 [/SUP], István Tombácz[SUP] 1 [/SUP], Emily Bettini[SUP] 2 [/SUP], Katlyn Lederer[SUP] 2 [/SUP], Chutamath Sittplangkoon[SUP] 3 [/SUP], Joel R Wilmore[SUP] 4 [/SUP], Brian T Gaudette[SUP] 4 [/SUP], Ousamah Y Soliman[SUP] 1 [/SUP], Matthew Pine[SUP] 1 [/SUP], Philip Hicks[SUP] 5 [/SUP], Tomaz B Manzoni[SUP] 2 [/SUP], James J Knox[SUP] 4 [/SUP], John L Johnson[SUP] 4 [/SUP], Dorottya Laczkó[SUP] 1 [/SUP], Hiromi Muramatsu[SUP] 1 [/SUP], Benjamin Davis[SUP] 1 [/SUP], Wenzhao Meng[SUP] 4 [/SUP], Aaron M Rosenfeld[SUP] 4 [/SUP], Shirin Strohmeier[SUP] 6 [/SUP], Paulo J C Lin[SUP] 7 [/SUP], Barbara L Mui[SUP] 7 [/SUP], Ying K Tam[SUP] 7 [/SUP], Katalin Karikó[SUP] 8 [/SUP], Alain Jacquet[SUP] 3 [/SUP], Florian Krammer[SUP] 6 [/SUP], Paul Bates[SUP] 2 [/SUP], Michael P Cancro[SUP] 4 [/SUP], Drew Weissman[SUP] 1 [/SUP], Eline T Luning Prak[SUP] 4 [/SUP], David Allman[SUP] 4 [/SUP], Michela Locci[SUP] 9 [/SUP], Norbert Pardi[SUP] 10 [/SUP]
Affiliations
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.
Keywords: IL-6; SARS-CoV-2; Tfh cell; adjuvant; germinal centers; influenza virus; lipid nanoparticle; vaccine.
. 2021 Nov 4;S1074-7613(21)00490-8.
doi: 10.1016/j.immuni.2021.11.001. Online ahead of print.
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Mohamad-Gabriel Alameh[SUP] 1 [/SUP], István Tombácz[SUP] 1 [/SUP], Emily Bettini[SUP] 2 [/SUP], Katlyn Lederer[SUP] 2 [/SUP], Chutamath Sittplangkoon[SUP] 3 [/SUP], Joel R Wilmore[SUP] 4 [/SUP], Brian T Gaudette[SUP] 4 [/SUP], Ousamah Y Soliman[SUP] 1 [/SUP], Matthew Pine[SUP] 1 [/SUP], Philip Hicks[SUP] 5 [/SUP], Tomaz B Manzoni[SUP] 2 [/SUP], James J Knox[SUP] 4 [/SUP], John L Johnson[SUP] 4 [/SUP], Dorottya Laczkó[SUP] 1 [/SUP], Hiromi Muramatsu[SUP] 1 [/SUP], Benjamin Davis[SUP] 1 [/SUP], Wenzhao Meng[SUP] 4 [/SUP], Aaron M Rosenfeld[SUP] 4 [/SUP], Shirin Strohmeier[SUP] 6 [/SUP], Paulo J C Lin[SUP] 7 [/SUP], Barbara L Mui[SUP] 7 [/SUP], Ying K Tam[SUP] 7 [/SUP], Katalin Karikó[SUP] 8 [/SUP], Alain Jacquet[SUP] 3 [/SUP], Florian Krammer[SUP] 6 [/SUP], Paul Bates[SUP] 2 [/SUP], Michael P Cancro[SUP] 4 [/SUP], Drew Weissman[SUP] 1 [/SUP], Eline T Luning Prak[SUP] 4 [/SUP], David Allman[SUP] 4 [/SUP], Michela Locci[SUP] 9 [/SUP], Norbert Pardi[SUP] 10 [/SUP]
Affiliations
- PMID: 34852217
- DOI: 10.1016/j.immuni.2021.11.001
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.
Keywords: IL-6; SARS-CoV-2; Tfh cell; adjuvant; germinal centers; influenza virus; lipid nanoparticle; vaccine.