Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection

Mark M Painter; Timothy S Johnston; Kendall A Lundgreen; Jefferson J S Santos; Juliana S Qin; Rishi R Goel; Sokratis A Apostolidis; Divij Mathew; Bria Fulmer; Justine C Williams; Michelle L McKeague; Ajinkya Pattekar; Ahmad Goode; Sean Nasta; Amy E Baxter; Josephine R Giles; Ashwin N Skelly; Laura E Felley; Maura McLaughlin; Joellen Weaver; Penn Medicine BioBank; Oliva Kuthuru; Jeanette Dougherty; Sharon Adamski; Sherea Long; Macy Kee; Cynthia Clendenin; Ricardo da Silva Antunes; Alba Grifoni; Daniela Weiskopf; Alessandro Sette; Alexander C Huang; Daniel J Rader; Scott E Hensley; Paul Bates; Allison R Greenplate; E John Wherry

doi:10.1038/s41590-023-01613-y

Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection

Nat Immunol. 2023 Oct;24(10):1711-1724. doi: 10.1038/s41590-023-01613-y. Epub 2023 Sep 21.

Authors

Mark M Painter^{1

2

3}, Timothy S Johnston^{1

4

5}, Kendall A Lundgreen⁶, Jefferson J S Santos⁶, Juliana S Qin³, Rishi R Goel^{1

2

3}, Sokratis A Apostolidis^{1

2

3

7}, Divij Mathew^{1

2}, Bria Fulmer^{1

2}, Justine C Williams³, Michelle L McKeague³, Ajinkya Pattekar³, Ahmad Goode³, Sean Nasta³, Amy E Baxter^{1

2}, Josephine R Giles^{1

2

8}, Ashwin N Skelly^{1

9}, Laura E Felley¹⁰, Maura McLaughlin^{1

2}, Joellen Weaver¹¹; Penn Medicine BioBank; Oliva Kuthuru^{1

2}, Jeanette Dougherty³, Sharon Adamski³, Sherea Long³, Macy Kee³, Cynthia Clendenin³, Ricardo da Silva Antunes¹², Alba Grifoni¹², Daniela Weiskopf¹², Alessandro Sette^{12

13}, Alexander C Huang^{1

8

14}, Daniel J Rader^{11

15}, Scott E Hensley⁶, Paul Bates⁶, Allison R Greenplate^{1

2

3}, E John Wherry^{16

17

18

19}

Collaborators

Affiliations

¹ Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
² Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
³ Immune Health, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
⁴ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
⁷ Division of Rheumatology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
⁸ Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
⁹ Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Division of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
¹¹ Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
¹² Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.
¹³ Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
¹⁴ Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
¹⁵ Penn Medicine Biobank, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
¹⁶ Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.
¹⁷ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.
¹⁸ Immune Health, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.
¹⁹ Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.

PMID: 37735592
DOI: 10.1038/s41590-023-01613-y

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific cluster of differentiation (CD)4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production and primary responses to nonspike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

Abstract

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