TY - JOUR
T1 - SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans
AU - SJTRC Study Team
AU - Mudd, Philip A.
AU - Minervina, Anastasia A.
AU - Pogorelyy, Mikhail V.
AU - Turner, Jackson S.
AU - Kim, Wooseob
AU - Kalaidina, Elizaveta
AU - Petersen, Jan
AU - Schmitz, Aaron J.
AU - Lei, Tingting
AU - Haile, Alem
AU - Kirk, Allison M.
AU - Mettelman, Robert C.
AU - Crawford, Jeremy Chase
AU - Nguyen, Thi H.O.
AU - Rowntree, Louise C.
AU - Rosati, Elisa
AU - Richards, Katherine A.
AU - Sant, Andrea J.
AU - Klebert, Michael K.
AU - Suessen, Teresa
AU - Middleton, William D.
AU - Estepp, Jeremie H.
AU - Schultz-Cherry, Stacey
AU - McGargill, Maureen A.
AU - Gaur, Aditya
AU - Hoffman, James
AU - Mori, Motomi
AU - Tang, Li
AU - Tuomanen, Elaine
AU - Webby, Richard
AU - Hayden, Randall T.
AU - Hakim, Hana
AU - Hijano, Diego R.
AU - Allison, Kim J.
AU - Allen, E. Kaitlynn
AU - Bajracharya, Resha
AU - Awad, Walid
AU - Van de Velde, Lee Ann
AU - Clark, Brandi L.
AU - Wilson, Taylor L.
AU - Souquette, Aisha
AU - Castellaw, Ashley
AU - Dallas, Ronald H.
AU - Gowen, Ashleigh
AU - Fabrizio, Thomas P.
AU - Lin, Chun Yang
AU - Brice, David C.
AU - Cherry, Sean
AU - Roubidoux, Ericka Kirkpatrick
AU - Cortez, Valerie
AU - Freiden, Pamela
AU - Wohlgemuth, Nicholas
AU - Whitt, Kendall
AU - Wolf, Joshua
AU - Teefey, Sharlene A.
AU - O'Halloran, Jane A.
AU - Presti, Rachel M.
AU - Kedzierska, Katherine
AU - Rossjohn, Jamie
AU - Thomas, Paul G.
AU - Ellebedy, Ali H.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/2/17
Y1 - 2022/2/17
N2 - SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1∗04-restricted response to S167–180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.
AB - SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1∗04-restricted response to S167–180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.
KW - CD4 T cell
KW - COVID-19
KW - SARS-CoV-2
KW - T follicular helper cell
KW - TCR repertoire
KW - human immunology
KW - lymph node
KW - mRNA vaccination
UR - http://www.scopus.com/inward/record.url?scp=85123021856&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2021.12.026
DO - 10.1016/j.cell.2021.12.026
M3 - Article
C2 - 35026152
AN - SCOPUS:85123021856
SN - 0092-8674
VL - 185
SP - 603-613.e15
JO - Cell
JF - Cell
IS - 4
ER -