TY - JOUR
T1 - SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation
AU - Lederer, Katlyn
AU - Castaño, Diana
AU - Gómez Atria, Daniela
AU - Oguin, Thomas H.
AU - Wang, Sidney
AU - Manzoni, Tomaz B.
AU - Muramatsu, Hiromi
AU - Hogan, Michael J.
AU - Amanat, Fatima
AU - Cherubin, Patrick
AU - Lundgreen, Kendall A.
AU - Tam, Ying K.
AU - Fan, Steven H.Y.
AU - Eisenlohr, Laurence C.
AU - Maillard, Ivan
AU - Weissman, Drew
AU - Bates, Paul
AU - Krammer, Florian
AU - Sempowski, Gregory D.
AU - Pardi, Norbert
AU - Locci, Michela
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/12/15
Y1 - 2020/12/15
N2 - The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms—mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant—looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses. Herein, Lederer et al. show a nucleic-acid-based vaccine platform for SARS-CoV-2 that potently induces germinal center (GC) responses. GCs are microanatomical sites harboring the formation of high-quality, protective antibody responses. Such vaccine platforms can be promising candidates to mitigate the COVID-19 pandemic.
AB - The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms—mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant—looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses. Herein, Lederer et al. show a nucleic-acid-based vaccine platform for SARS-CoV-2 that potently induces germinal center (GC) responses. GCs are microanatomical sites harboring the formation of high-quality, protective antibody responses. Such vaccine platforms can be promising candidates to mitigate the COVID-19 pandemic.
KW - COVID-19
KW - SARS-CoV-2
KW - T follicular helper cells
KW - germinal center B cells
KW - germinal centers
KW - mRNA vaccines
KW - neutralizing antibodies
UR - http://www.scopus.com/inward/record.url?scp=85097681435&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2020.11.009
DO - 10.1016/j.immuni.2020.11.009
M3 - Article
C2 - 33296685
AN - SCOPUS:85097681435
SN - 1074-7613
VL - 53
SP - 1281-1295.e5
JO - Immunity
JF - Immunity
IS - 6
ER -