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Preserved T cell reactivity to the SARS-CoV-2 Omicron variant indicates continued protection in vaccinated individuals

View ORCID ProfileLorenzo De Marco, View ORCID ProfileSilvia D’Orso, View ORCID ProfileMarta Pirronello, View ORCID ProfileAlice Verdiani, View ORCID ProfileAndrea Termine, View ORCID ProfileCarlo Fabrizio, View ORCID ProfileAlessia Capone, View ORCID ProfileAndrea Sabatini, View ORCID ProfileGisella Guerrera, View ORCID ProfileRoberta Placido, View ORCID ProfileManolo Sambucci, View ORCID ProfileDaniela F. Angelini, View ORCID ProfileFlavia Giannessi, View ORCID ProfileMario Picozza, View ORCID ProfileCarlo Caltagirone, View ORCID ProfileAntonino Salvia, View ORCID ProfileElisabetta Volpe, View ORCID ProfileMaria Pia Balice, View ORCID ProfileAngelo Rossini, View ORCID ProfileOlaf Rötzschke, View ORCID ProfileEmiliano Giardina, View ORCID ProfileLuca Battistini, View ORCID ProfileGiovanna Borsellino, Santa Lucia Foundation, Rome, Italy
doi: https://doi.org/10.1101/2021.12.30.474453
Lorenzo De Marco
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Silvia D’Orso
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Marta Pirronello
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Alice Verdiani
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Andrea Termine
2Data Science Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Carlo Fabrizio
2Data Science Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Alessia Capone
3Molecular Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Andrea Sabatini
3Molecular Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Gisella Guerrera
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Roberta Placido
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Manolo Sambucci
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Daniela F. Angelini
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Flavia Giannessi
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Mario Picozza
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Carlo Caltagirone
4Department of Clinical and Behavioral Neurology, Santa Lucia Foundation IRCCS; Rome, Italy
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Antonino Salvia
5Medical Services, Santa Lucia Foundation IRCCS; Rome, Italy
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Elisabetta Volpe
3Molecular Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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Maria Pia Balice
6Clinical Microbiology Laboratory, Santa Lucia Foundation IRCCS; Rome, Italy
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Angelo Rossini
5Medical Services, Santa Lucia Foundation IRCCS; Rome, Italy
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Olaf Rötzschke
7Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore
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Emiliano Giardina
8Genomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, Rome, Italy
9Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
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Luca Battistini
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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  • For correspondence: g.borsellino@hsantalucia.it l.battistini@hsantalucia.it
Giovanna Borsellino
1Neuroimmunology Unit, Santa Lucia Foundation IRCCS; Rome, Italy
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  • ORCID record for Giovanna Borsellino
  • For correspondence: g.borsellino@hsantalucia.it l.battistini@hsantalucia.it
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Abstract

Importance The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from convalescent or vaccinated individuals imposes the study of cellular immunity to predict the degree of immune protection to the yet again new coronavirus.

Design Prospective monocentric observational study.

Setting Conducted between December 20-21 at the Santa Lucia Foundation IRCCS.

Participants 61 volunteers (Mean age 41.62, range 21-62; 38F/23M) with different vaccination and SARS-CoV-2 infection backgrounds donated 15 ml of blood. Of these donors, one had recently completed chemotherapy, and one was undergoing treatment with monoclonal antibodies; the others reported no known health issue.

Main Outcome(s) and Measure(s) The outcomes were the measurement of T cell reactivity to the mutated regions of the Spike protein of the Omicron SARS-CoV-2 variant and the assessment of remaining T cell immunity to the spike protein by stimulation with peptide libraries.

Results Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the Spike protein of SARS-CoV-2. T cell responses to peptides covering the mutated regions in the Omicron variant were decreased by over 47% compared to the same regions of the ancestral vaccine strain. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 83%). No significant differences in loss of immune recognition were identified between groups of donors with different vaccination and/or infection histories.

Conclusions and Relevance We conclude that despite the mutations in the Spike protein, the SARS-CoV-2 Omicron variant is nonetheless recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease is maintained.

Question Does the Omicron variant of SARS-CoV-2 escape cellular immunity?

Findings This observational study was performed on 61 vaccinated donors with established immunity to SARS-CoV-2. Cellular responses to the mutated regions of the Omicron Spike protein were detected in 80% of donors. The mutations reduced T cell recognition by 47% compared to the vaccine strain. Reactivity to the whole Spike protein, however, was present in 100% of donors, and the fraction of remaining immunity to SARS-CoV-2 was estimated to be 83%.

Meaning Cellular immunity to the Omicron variant is maintained despite the mutations in its Spike protein, and may thus confer protection from severe COVID-19 in vaccinated individuals.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 30, 2021.
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Preserved T cell reactivity to the SARS-CoV-2 Omicron variant indicates continued protection in vaccinated individuals
Lorenzo De Marco, Silvia D’Orso, Marta Pirronello, Alice Verdiani, Andrea Termine, Carlo Fabrizio, Alessia Capone, Andrea Sabatini, Gisella Guerrera, Roberta Placido, Manolo Sambucci, Daniela F. Angelini, Flavia Giannessi, Mario Picozza, Carlo Caltagirone, Antonino Salvia, Elisabetta Volpe, Maria Pia Balice, Angelo Rossini, Olaf Rötzschke, Emiliano Giardina, Luca Battistini, Giovanna Borsellino, Santa Lucia Foundation, Rome, Italy
bioRxiv 2021.12.30.474453; doi: https://doi.org/10.1101/2021.12.30.474453
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Preserved T cell reactivity to the SARS-CoV-2 Omicron variant indicates continued protection in vaccinated individuals
Lorenzo De Marco, Silvia D’Orso, Marta Pirronello, Alice Verdiani, Andrea Termine, Carlo Fabrizio, Alessia Capone, Andrea Sabatini, Gisella Guerrera, Roberta Placido, Manolo Sambucci, Daniela F. Angelini, Flavia Giannessi, Mario Picozza, Carlo Caltagirone, Antonino Salvia, Elisabetta Volpe, Maria Pia Balice, Angelo Rossini, Olaf Rötzschke, Emiliano Giardina, Luca Battistini, Giovanna Borsellino, Santa Lucia Foundation, Rome, Italy
bioRxiv 2021.12.30.474453; doi: https://doi.org/10.1101/2021.12.30.474453

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