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

Mohamad Gabriel Alameh; István Tombácz; Emily Bettini; Katlyn Lederer; Chutamath Sittplangkoon; Joel R. Wilmore; Brian T. Gaudette; Ousamah Y. Soliman; Matthew Pine; Philip Hicks; Tomaz B. Manzoni; James J. Knox; John L. Johnson; Dorottya Laczkó; Hiromi Muramatsu; Benjamin Davis; Wenzhao Meng; Aaron M. Rosenfeld; Shirin Strohmeier; Paulo J.C. Lin; Barbara L. Mui; Ying K. Tam; Katalin Karikó; Alain Jacquet; Florian Krammer; Paul Bates; Michael P. Cancro; Drew Weissman; Eline T. Luning Prak; David Allman; Michela Locci; Norbert Pardi

doi:10.1016/j.immuni.2021.11.001

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

Mohamad Gabriel Alameh, István Tombácz, Emily Bettini, Katlyn Lederer, Chutamath Sittplangkoon, Joel R. Wilmore, Brian T. Gaudette, Ousamah Y. Soliman, Matthew Pine, Philip Hicks, Tomaz B. Manzoni, James J. Knox, John L. Johnson, Dorottya Laczkó, Hiromi Muramatsu, Benjamin Davis, Wenzhao Meng, Aaron M. Rosenfeld, Shirin Strohmeier, Paulo J.C. LinBarbara L. Mui, Ying K. Tam, Katalin Karikó, Alain Jacquet, Florian Krammer, Paul Bates, Michael P. Cancro, Drew Weissman, Eline T. Luning Prak, David Allman, Michela Locci, Norbert Pardi

Research output: Contribution to journal › Article › peer-review

401 Scopus citations

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.

Original language	English
Pages (from-to)	2877-2892.e7
Journal	Immunity
Volume	54
Issue number	12
DOIs	https://doi.org/10.1016/j.immuni.2021.11.001
State	Published - 14 Dec 2021

Keywords

IL-6
SARS-CoV-2
Tfh cell
adjuvant
germinal centers
influenza virus
lipid nanoparticle
vaccine

Access to Document

10.1016/j.immuni.2021.11.001

Cite this

Alameh, M. G., Tombácz, I., Bettini, E., Lederer, K., Sittplangkoon, C., Wilmore, J. R., Gaudette, B. T., Soliman, O. Y., Pine, M., Hicks, P., Manzoni, T. B., Knox, J. J., Johnson, J. L., Laczkó, D., Muramatsu, H., Davis, B., Meng, W., Rosenfeld, A. M., Strohmeier, S., ... Pardi, N. (2021). Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity, 54(12), 2877-2892.e7. https://doi.org/10.1016/j.immuni.2021.11.001

@article{8814664eabb142ddabfb8bdad2d56570,

title = "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.",

keywords = "IL-6, SARS-CoV-2, Tfh cell, adjuvant, germinal centers, influenza virus, lipid nanoparticle, vaccine",

author = "Alameh, {Mohamad Gabriel} and Istv{\'a}n Tomb{\'a}cz and Emily Bettini and Katlyn Lederer and Chutamath Sittplangkoon and Wilmore, {Joel R.} and Gaudette, {Brian T.} and Soliman, {Ousamah Y.} and Matthew Pine and Philip Hicks and Manzoni, {Tomaz B.} and Knox, {James J.} and Johnson, {John L.} and Dorottya Laczk{\'o} and Hiromi Muramatsu and Benjamin Davis and Wenzhao Meng and Rosenfeld, {Aaron M.} and Shirin Strohmeier and Lin, {Paulo J.C.} and Mui, {Barbara L.} and Tam, {Ying K.} and Katalin Karik{\'o} and Alain Jacquet and Florian Krammer and Paul Bates and Cancro, {Michael P.} and Drew Weissman and {Luning Prak}, {Eline T.} and David Allman and Michela Locci and Norbert Pardi",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = dec,

day = "14",

doi = "10.1016/j.immuni.2021.11.001",

language = "English",

volume = "54",

pages = "2877--2892.e7",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "12",

}

Alameh, MG, Tombácz, I, Bettini, E, Lederer, K, Sittplangkoon, C, Wilmore, JR, Gaudette, BT, Soliman, OY, Pine, M, Hicks, P, Manzoni, TB, Knox, JJ, Johnson, JL, Laczkó, D, Muramatsu, H, Davis, B, Meng, W, Rosenfeld, AM, Strohmeier, S, Lin, PJC, Mui, BL, Tam, YK, Karikó, K, Jacquet, A, Krammer, F, Bates, P, Cancro, MP, Weissman, D, Luning Prak, ET, Allman, D, Locci, M & Pardi, N 2021, 'Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses', Immunity, vol. 54, no. 12, pp. 2877-2892.e7. https://doi.org/10.1016/j.immuni.2021.11.001

TY - JOUR

T1 - Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses

AU - Alameh, Mohamad Gabriel

AU - Tombácz, István

AU - Bettini, Emily

AU - Lederer, Katlyn

AU - Sittplangkoon, Chutamath

AU - Wilmore, Joel R.

AU - Gaudette, Brian T.

AU - Soliman, Ousamah Y.

AU - Pine, Matthew

AU - Hicks, Philip

AU - Manzoni, Tomaz B.

AU - Knox, James J.

AU - Johnson, John L.

AU - Laczkó, Dorottya

AU - Muramatsu, Hiromi

AU - Davis, Benjamin

AU - Meng, Wenzhao

AU - Rosenfeld, Aaron M.

AU - Strohmeier, Shirin

AU - Lin, Paulo J.C.

AU - Mui, Barbara L.

AU - Tam, Ying K.

AU - Karikó, Katalin

AU - Jacquet, Alain

AU - Krammer, Florian

AU - Bates, Paul

AU - Cancro, Michael P.

AU - Weissman, Drew

AU - Luning Prak, Eline T.

AU - Allman, David

AU - Locci, Michela

AU - Pardi, Norbert

PY - 2021/12/14

Y1 - 2021/12/14

N2 - 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.

AB - 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.

KW - IL-6

KW - SARS-CoV-2

KW - Tfh cell

KW - adjuvant

KW - germinal centers

KW - influenza virus

KW - lipid nanoparticle

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85120409484&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2021.11.001

DO - 10.1016/j.immuni.2021.11.001

M3 - Article

C2 - 34852217

AN - SCOPUS:85120409484

SN - 1074-7613

VL - 54

SP - 2877-2892.e7

JO - Immunity

JF - Immunity

IS - 12

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this