Summary
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 show that frequency of TFH correlates with that of S-binding germinal center B cells. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLADPB1* 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.
Competing Interest Statement
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, LLC and Fimbrion Therapeutics and is the founder of ImmuneBio Consulting LLC. 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.
Footnotes
↵11 Jeremie H. Estepp, Stacey Schultz-Cherry, Maureen A. McGargill, Aditya Gaur, James Hoffman, Motomi Mori, Li Tang, Elaine Tuomanen, Richard Webby, Randall T. Hayden, Hana Hakim, Diego R. Hijano, Kim J. Allison, E. Kaitlynn Allen, Resha Bajracharya, Walid Awad, Lee-Ann Van de Velde, Brandi L Clark, Taylor L. Wilson, Aisha Souquette, Ashley Castellaw, Ronald H. Dallas, Ashleigh Gowen, Thomas P. Fabrizio, Chun-Yang Lin, David C. Brice, Sean Cherry, Ericka Kirkpatrick Roubidoux, Valerie Cortez, Pamela Freiden, Nicholas Wohlgemuth, Kendall Whitt;
↵16 These authors contributed equally
