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

被引：449

作者：

Alameh, Mohamad-Gabriel ^{[1
]}

Tombacz, Istvan ^{[1
]}

Bettini, Emily ^{[2
]}

Lederer, Katlyn ^{[2
]}

Sittplangkoon, Chutamath ^{[3
]}

Wilmore, Joel R. ^{[4
]}

Gaudette, Brian T. ^{[4
]}

Soliman, Ousamah Y. ^{[1
]}

Pine, Matthew ^{[1
]}

Hicks, Philip ^{[2
,5
]}

Manzoni, Tomaz B. ^{[2
]}

Knox, James J. ^{[4
]}

Johnson, John L. ^{[4
]}

Laczko, Dorottya ^{[1
]}

Muramatsu, Hiromi ^{[1
]}

Davis, Benjamin ^{[1
]}

Meng, Wenzhao ^{[4
]}

Rosenfeld, Aaron M. ^{[4
]}

Strohmeier, Shirin ^{[6
]}

Lin, Paulo J. C. ^{[7
]}

Mui, Barbara L. ^{[7
]}

Tam, Ying K. ^{[7
]}

Kariko, Katalin ^{[1
,8
]}

Jacquet, Alain ^{[3
]}

Krammer, Florian ^{[6
]}

Bates, Paul ^{[2
]}

Cancro, Michael P. ^{[4
]}

Weissman, Drew ^{[1
]}

Prak, Eline T. Luning ^{[4
]}

Allman, David ^{[4
]}

Locci, Michela ^{[2
]}

Pardi, Norbert ^{[1
]}

机构：

[1] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[3] Chulalongkorn Univ, Fac Med, Ctr Excellence Vaccine Res & Dev, Bangkok, Thailand

[4] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA

[6] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[7] Acuitas Therapeut, Vancouver, BC, Canada

[8] BioNTech RNA Pharmaceut, Mainz, Germany

来源：

IMMUNITY | 2021年 / 54卷 / 12期

关键词：

GERMINAL CENTER RESPONSES; TOLL-LIKE RECEPTORS; B-CELL; IMMUNE-RESPONSE; DIFFERENTIATION; INNATE; MICE; BCL6; POLARIZATION; GENERATION;

D O I：

10.1016/j.immuni.2021.11.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：2877 / +

页数：24

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