Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses
Abstract
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 08, 2018
- Source ID
- 10.1084/jem.20171450
Entities
People
- Arpita Myles
- Barbara L. Mui
- Barton Haynes
- Bette Korber
- Celia C LaBranche
- Charles Li
- Daniel A. Balikov
- David C. Montefiori
- Derek W. Cain
- Drew Weissman
- Elinor Willis
- Florian Krammer
- Hans P. Verkerke
- Hiromi Muramatsu
- Houping Ni
- Hua-Xin Liao
- István Tombácz
- Jenna L. Lobby
- Kaela Parkhouse
- Katalin Karikó
- Kelly K. Lee
- Kevin O Saunders
- Laura L Sutherland
- Laurence C. Eisenlohr
- Letitia Jones
- M Anthony Moody
- Mark G. Lewis
- Martin S. Naradikian
- Michael J. Hogan
- Michael J. Hope
- Michael P Cancro
- Norbert Pardi
- Patricia Polacino
- Peter T. Hraber
- Richard M Scearce
- Scott E Hensley
- Shiu-lok Hu
- Thomas D. Madden
- Ying K. Tam
Organizations
- Center for Global Health
- Children's Hospital of Philadelphia
- Duke University
- Duke University Hospital
- Gates Foundation
- Icahn School of Medicine at Mount Sinai
- Los Alamos National Laboratory
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Takeda (United States)
- United States Department of Defense
- University of Pennsylvania
- University of Washington