Journal article
SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection
LC Rowntree, THO Nguyen, L Kedzierski, MR Neeland, J Petersen, JC Crawford, LF Allen, EB Clemens, B Chua, HA McQuilten, AA Minervina, MV Pogorelyy, P Chaurasia, HX Tan, AK Wheatley, X Jia, F Amanat, F Krammer, EK Allen, S Sonda Show all
Immunity | Published : 2022
Abstract
As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in ch..
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Grants
Awarded by Australian Research Council
Funding Acknowledgements
We thank the participating families involved in the study and Kate Dohle, Jill Nguyen, Isabella Overmars, Philip Sutton, and Daniel Pellicci for their support with the cohorts. We thank the Melbourne Cytometry Platform for the technical assistance. This work was supported by the NHMRC Leadership Investigator Grant to K.K. (1173871) ; the NHMRC Emerging Leadership Level 1 Investigator Grant to T.H.O.N. (#1194036) and A.K.W. (#1173433) ; the Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to K.K.; the Doherty Collaborative Seed grant to M.R.N., A.K.W., S.J.K., S.T., C.E.v.d.S., and K.K.; the Victorian Government (S.J.K. and A.K.W.) ; the Clifford Craig Foundation Project Grant to K.L.F. and K.K. (#186) ; the MRFF award (#2002073) to S.J.K. and A.K.W.; the MRFF Award (#1202445) to K.K.; the MRFF Award (#2005544) to K.K., S.J.K., and A.K.W.; the NHMRC program grant 1149990 (S.J.K.) ; the NHMRC project grant 1162760 (A.K.W.) ; the NIH contract CIVC-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K.; and the NIAID UO1 grant 1U01AI144616-01 ?Dissection of Influenza Vaccination and Infection for Childhood Immunity? (DIVINCI) to F.K., P.G.T., K.K., and P.S.P. S.J.K. is supported by the NHMRC Senior Prin-cipal Research Fellowship (#1136322) . C.E.v.d.S. received funding from the European Union?s Horizon 2020 research program under the Marie Sk1odow-ska-Curie grant agreement (#792532) and is supported by the ARC-DECRA Fellowship (#DE200100185) and University of Melbourne Establishment grant. J.R. is supported by an ARC Laureate Fellowship. J.C.C. and P.G.T. are sup-ported by the NIH NIAID R01 AI136514-03 and the ALSAC at St. Jude. P.V.L. is supported by an NHMRC Career Development Fellowship. Work in the F.K. laboratory was partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, #HHSN272201400008C) , the Centers of Excellence for Influenza Research and Response (CEIRR, #75N93021C00014) , by the Collaborative Influenza Vaccine Innovation Cen-ters (CIVICs, #75N93019C00051) , and by institutional funds. We acknowledge the RCH Foundation for their support of the study and recruitment of the fam-ilies involved. Recruitment of the household contacts was enable by COVID-19 Grant, Department of Jobs, Precincts and Regions, Victoria State Government and Research Grant, DHB Foundation, Australia. The graphical abstract was created with BioRender.com .