Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 603-613.e15 |
| Number of pages | 27 |
| Journal | Cell |
| Volume | 185 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 17 Feb 2022 |
Keywords
- CD4 T cell
- COVID-19
- human immunology
- lymph node
- mRNA vaccination
- SARS-CoV-2
- T follicular helper cell
- TCR repertoire
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In: Cell, Vol. 185, No. 4, 17.02.2022, p. 603-613.e15.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans
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 - SJTRC Study Team
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 - Funding Information: The authors would like to thank the study participants for their invaluable contribution to this work. We also thank Greig Lennon from St. Jude Immunology flow core for his help with FACS, Hartwell Center at St. Jude Children's Research Hospital for high-throughput sequencing, and Carmen Llerna for assistance in HLA-DP4 protein purification. This study was funded in part by the Washington University Institute for Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) (P.A.M.). J.R. is supported by an Australian Research Council Laureate Fellowship. K.K. was supported by the NHMRC Leadership Investigator Fellowship (#1173871), and T.H.O.N. was supported by the NHMRC Emerging Leadership Level 1 Investigator Fellowship (#1194036). This work was funded by ALSAC at St. Jude; the Center for Influenza Vaccine Research for High-Risk Populations (CIVR-HRP) contract number 75N93019C00052 (P.G.T. and K.K.); the St. Jude Center of Excellence for Influenza Research and Surveillance (P.G.T.) contract number HHSN272201400006C; and the St. Jude Center of Excellence for Influenza Research and Response (P.G.T.) contract numbers 75N93021C00016, U01AI150747, U01AI144616-02S1, and R01AI136514 (P.G.T.). The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747, NIAID Centers of Excellence for Influenza Research and Surveillance contracts HHSN272201400006C and HHSN272201400008C, and by NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIAID or NIH. Conceptualization: P.A.M. A.A.M. M.V.P. P.G.T. and A.H.E.; methodology: P.A.M. A.A.M. M.V.P. J.S.T. J.P. J.C.C. M.K.K. S.A.T. J.A.O. R.M.P. P.G.T. and A.H.E.; investigation: P.A.M. A.A.M. M.V.P. J.S.T. W.K. E.K. J.P. A.J. Schmitz, T.L. A.H. A.M.K. R.C.M. J.C.C. T.H.O.N. L.C.R. E.R. K.A.R. A.J. Sant, T.S. W.D.M. and S.A.T.; formal analysis: P.A.M. A.A.M. M.V.P. and J.C.C.; visualization: P.A.M. A.A.M. M.V.P. and R.C.M.; resources: SJTRC Study Team; Data curation: J.C.C. J.W. and SJTRC Study Team; funding acquisition: P.A.M. P.G.T. and A.H.E.; supervision: P.A.M. S.A.T. J.A.O. R.M.P. K.K. J.R. P.G.T. and A.H.E.; writing ? original draft: P.A.M. A.A.M. and M.V.P.; writing ? review & editing: all co-authors. The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. A.H.E. has received consulting payments from Mubadala Investment Company, InBios International, and Fimbrion Therapeutics and is the founder of ImmuneBio Consulting. P.G.T. has consulted and/or received honoraria and travel support from Illumina, Johnson and Johnson, and 10X Genomics. P.G.T. serves on the Scientific Advisory Board of Immunoscape and Cytoagents. The authors have applied for patents covering some aspects of these studies. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. Funding Information: The authors would like to thank the study participants for their invaluable contribution to this work. We also thank Greig Lennon from St. Jude Immunology flow core for his help with FACS, Hartwell Center at St. Jude Children’s Research Hospital for high-throughput sequencing, and Carmen Llerna for assistance in HLA-DP4 protein purification. This study was funded in part by the Washington University Institute for Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) (P.A.M.). J.R. is supported by an Australian Research Council Laureate Fellowship. K.K. was supported by the NHMRC Leadership Investigator Fellowship (# 1173871 ), and T.H.O.N. was supported by the NHMRC Emerging Leadership Level 1 Investigator Fellowship (# 1194036 ). This work was funded by ALSAC at St. Jude; the Center for Influenza Vaccine Research for High-Risk Populations (CIVR-HRP) contract number 75N93019C00052 (P.G.T. and K.K.); the St. Jude Center of Excellence for Influenza Research and Surveillance (P.G.T.) contract number HHSN272201400006C ; and the St. Jude Center of Excellence for Influenza Research and Response (P.G.T.) contract numbers 75N93021C00016 , U01AI150747 , U01AI144616-02S1 , and R01AI136514 (P.G.T.). The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747 , NIAID Centers of Excellence for Influenza Research and Surveillance contracts HHSN272201400006C and HHSN272201400008C , and by NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051 . The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIAID or NIH. 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 - human immunology
KW - lymph node
KW - mRNA vaccination
KW - SARS-CoV-2
KW - T follicular helper cell
KW - TCR repertoire
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 -