作者
Mohamad‐Gabriel Alameh,István Tombácz,Emily Bettini,Katlyn Lederer,Sonia Ndeupen,Chutamath Sittplangkoon,Joel R. Wilmore,Brian T. Gaudette,Ousamah Younoss 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,Botond Z. Igyártó,Michela Locci,Norbert Pardi
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.