St. Jude Research

Methods for detecting COVID Infection, vaccination response and to compare vaccine potency (SJ-22-0003)

St. Jude Reference #SJ-22-0003

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, researchers at St. Jude 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 and can provide an easy way to access CD4 T cell memory responses in more than half of the worldwide population. Collectively, the results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

The researchers utilize TCRalpha, instead of TCRbeta chain TCR repertoire sequencing (like the T-Detect test from Adaptive Biotechnologies), as the single alpha chain TCR motif identifies memory CD4 T cells after SARS-CoV-2 infection or importantly, vaccination with high specificity, and it recognizes an immunodominant epitope present in all DPB1*04:01/04:02 individuals. Thus, unlike other tests for T cell immunity we know exactly the limitation of this test (having appropriate HLA alleles), while others don’t account for HLA-diversity to get the result.

The T cell response to this epitope can be found by using any of the following methods:

  • bulk DNA or RNA-based TCR alpha repertoire sequencing of the whole blood, fine needle LN aspirates or other lymphoid tissues 
  • single cell TCR sequencing 
  • Targeted PCR amplification of this specific region of the TCR
  • MHC-multimer (DPB1:04 HLA loaded with the epitope) staining of human samples, with and without subsequent sequencing of TCR receptors.  

MHC-multimer staining combined with other surface markers of T cells can also provide information about the quality of these memory T cells. This can be important to: 

  1. Detect responses to SARS-CoV-2 vaccination or infection in immunocompromised patients with impaired antibody responses
  2. Provide the information about longevity of cellular memory responses after natural infection and vaccination
  3. Can be used to compare the potency of different vaccines to elicit CD4 T cell responses
  4. Can be used to detect a current or recent COVID-19 infection

Keywords

COVID-19; T follicular helper cell; lymph node; CD4+ T cell; mRNA vaccination; TCR repertoire; SARS-CoV-2; human immunology

Granted Patents or Published Applications

Related Scientific References

Philip A. Mudd, Anastasia A. Minervina, Mikhail V. Pogorelyy, Jackson S. Turner, Wooseob Kim, Elizaveta Kalaidina, Jan Petersen, Aaron J. Schmitz, Tingting Lei, Alem Haile, Allison M. Kirk, Robert C. Mettelman, Jeremy Chase Crawford, Thi H.O. Nguyen, Louise C. Rowntree, Elisa Rosati, Katherine A. Richards, Andrea J. Sant, Michael K. Klebert, Teresa Suessen, William D. Middleton, 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, Joshua Wolf, Sharlene A. Teefey, Jane A. O’Halloran, Rachel M. Presti, Katherine Kedzierska, Jamie Rossjohn, Paul G. Thomas, Ali H. Ellebedy, “SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans,” Cell,

Volume 185, Issue 4, 2022, Pages 603-613.e15, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2021.12.026.

https://www.sciencedirect.com/science/article/pii/S0092867421014896

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