IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31721-6.html
   My bibliography  Save this article

A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection

Author

Listed:
  • Iris N. Pardieck

    (Leiden University Medical Center)

  • Tetje C. van der Sluis

    (Leiden University Medical Center)

  • Esmé T. I. van der Gracht

    (Leiden University Medical Center)

  • Dominique M. B. Veerkamp

    (Leiden University Medical Center)

  • Felix M. Behr

    (Leiden University Medical Center)

  • Suzanne van Duikeren

    (Leiden University Medical Center)

  • Guillaume Beyrend

    (Leiden University Medical Center)

  • Jasper Rip

    (Leiden University Medical Center)

  • Reza Nadafi

    (Leiden University Medical Center)

  • Elham Beyranvand Nejad

    (Leiden University Medical Center)

  • Nils Mülling

    (Leiden University Medical Center)

  • Dena J. Brasem

    (Leiden University Medical Center)

  • Marcel G. M. Camps

    (Leiden University Medical Center)

  • Sebenzile K. Myeni

    (Leiden University Medical Center)

  • Peter J. Bredenbeek

    (Leiden University Medical Center)

  • Marjolein Kikkert

    (Leiden University Medical Center)

  • Yeonsu Kim

    (Helmholtz Centre for Infection Research)

  • Luka Cicin-Sain

    (Helmholtz Centre for Infection Research)

  • Tamim Abdelaal

    (Delft University of Technology
    Leiden University Medical Center)

  • Klaas P. J. M. van Gisbergen

    (Sanquin Research and Landsteiner Laboratory)

  • Kees L. M. C. Franken

    (Leiden University Medical Center)

  • Jan Wouter Drijfhout

    (Leiden University Medical Center)

  • Cornelis J. M. Melief

    (ISA Pharmaceuticals BV)

  • Gerben C. M. Zondag

    (Immunetune BV)

  • Ferry Ossendorp

    (Leiden University Medical Center)

  • Ramon Arens

    (Leiden University Medical Center)

Abstract

Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8+ T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8+ T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8+ effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8+ T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.

Suggested Citation

  • Iris N. Pardieck & Tetje C. van der Sluis & Esmé T. I. van der Gracht & Dominique M. B. Veerkamp & Felix M. Behr & Suzanne van Duikeren & Guillaume Beyrend & Jasper Rip & Reza Nadafi & Elham Beyranvan, 2022. "A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31721-6
    DOI: 10.1038/s41467-022-31721-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31721-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31721-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chek Meng Poh & Guillaume Carissimo & Bei Wang & Siti Naqiah Amrun & Cheryl Yi-Pin Lee & Rhonda Sin-Ling Chee & Siew-Wai Fong & Nicholas Kim-Wah Yeo & Wen-Hsin Lee & Anthony Torres-Ruesta & Yee-Sin Le, 2020. "Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients," Nature Communications, Nature, vol. 11(1), pages 1-7, December.
    2. Katherine McMahan & Jingyou Yu & Noe B. Mercado & Carolin Loos & Lisa H. Tostanoski & Abishek Chandrashekar & Jinyan Liu & Lauren Peter & Caroline Atyeo & Alex Zhu & Esther A. Bondzie & Gabriel Dagott, 2021. "Correlates of protection against SARS-CoV-2 in rhesus macaques," Nature, Nature, vol. 590(7847), pages 630-634, February.
    3. Julian Braun & Lucie Loyal & Marco Frentsch & Daniel Wendisch & Philipp Georg & Florian Kurth & Stefan Hippenstiel & Manuela Dingeldey & Beate Kruse & Florent Fauchere & Emre Baysal & Maike Mangold & , 2020. "SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19," Nature, Nature, vol. 587(7833), pages 270-274, November.
    4. Delphine Planas & David Veyer & Artem Baidaliuk & Isabelle Staropoli & Florence Guivel-Benhassine & Maaran Michael Rajah & Cyril Planchais & Françoise Porrot & Nicolas Robillard & Julien Puech & Matth, 2021. "Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization," Nature, Nature, vol. 596(7871), pages 276-280, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Laurent Renia & Yun Shan Goh & Angeline Rouers & Nina Bert & Wan Ni Chia & Jean-Marc Chavatte & Siew‐Wai Fong & Zi Wei Chang & Nicole Ziyi Zhuo & Matthew Zirui Tay & Yi-Hao Chan & Chee Wah Tan & Nicho, 2022. "Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Rúbens Prince dos Santos Alves & Julia Timis & Robyn Miller & Kristen Valentine & Paolla Beatriz Almeida Pinto & Andrew Gonzalez & Jose Angel Regla-Nava & Erin Maule & Michael N. Nguyen & Norazizah Sh, 2024. "Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Elham Khatamzas & Markus H. Antwerpen & Alexandra Rehn & Alexander Graf & Johannes Christian Hellmuth & Alexandra Hollaus & Anne-Wiebe Mohr & Erik Gaitzsch & Tobias Weiglein & Enrico Georgi & Clemens , 2022. "Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Aloysious Ssemaganda & Huong Mai Nguyen & Faisal Nuhu & Naima Jahan & Catherine M. Card & Sandra Kiazyk & Giulia Severini & Yoav Keynan & Ruey-Chyi Su & Hezhao Ji & Bernard Abrenica & Paul J. McLaren , 2022. "Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    5. Adriana Tomic & Donal T. Skelly & Ane Ogbe & Daniel O’Connor & Matthew Pace & Emily Adland & Frances Alexander & Mohammad Ali & Kirk Allott & M. Azim Ansari & Sandra Belij-Rammerstorfer & Sagida Bibi , 2022. "Divergent trajectories of antiviral memory after SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    6. Byung Uk Lee, 2021. "Why Does the SARS-CoV-2 Delta VOC Spread So Rapidly? Universal Conditions for the Rapid Spread of Respiratory Viruses, Minimum Viral Loads for Viral Aerosol Generation, Effects of Vaccination on Viral," IJERPH, MDPI, vol. 18(18), pages 1-6, September.
    7. Haogao Gu & Ahmed Abdul Quadeer & Pavithra Krishnan & Daisy Y. M. Ng & Lydia D. J. Chang & Gigi Y. Z. Liu & Samuel M. S. Cheng & Tommy T. Y. Lam & Malik Peiris & Matthew R. McKay & Leo L. M. Poon, 2023. "Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Haisheng Yu & Banghui Liu & Yudi Zhang & Xijie Gao & Qian Wang & Haitao Xiang & Xiaofang Peng & Caixia Xie & Yaping Wang & Peiyu Hu & Jingrong Shi & Quan Shi & Pingqian Zheng & Chengqian Feng & Guofan, 2023. "Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Li Wang & Markus H. Kainulainen & Nannan Jiang & Han Di & Gaston Bonenfant & Lisa Mills & Michael Currier & Punya Shrivastava-Ranjan & Brenda M. Calderon & Mili Sheth & Brian R. Mann & Jaber Hossain &, 2022. "Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    10. Matthew R. Chang & Luke Tomasovic & Natalia A. Kuzmina & Adam J. Ronk & Patrick O. Byrne & Rebecca Johnson & Nadia Storm & Eduardo Olmedillas & Yixuan J. Hou & Alexandra Schäfer & Sarah R. Leist & Lon, 2022. "IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Hassen Kared & Asia-Sophia Wolf & Amin Alirezaylavasani & Anthony Ravussin & Guri Solum & Trung The Tran & Fridtjof Lund-Johansen & John Torgils Vaage & Lise Sofie Nissen-Meyer & Unni C. Nygaard & Ola, 2022. "Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Suman Das & Janmejay Singh & Heena Shaman & Balwant Singh & Anbalagan Anantharaj & Patil Sharanabasava & Rajesh Pandey & Rakesh Lodha & Anil Kumar Pandey & Guruprasad R. Medigeshi, 2022. "Pre-existing antibody levels negatively correlate with antibody titers after a single dose of BBV152 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    13. Dapeng Li & David R. Martinez & Alexandra Schäfer & Haiyan Chen & Maggie Barr & Laura L. Sutherland & Esther Lee & Robert Parks & Dieter Mielke & Whitney Edwards & Amanda Newman & Kevin W. Bock & Mahn, 2022. "Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Biao Zhou & Runhong Zhou & Bingjie Tang & Jasper Fuk-Woo Chan & Mengxiao Luo & Qiaoli Peng & Shuofeng Yuan & Hang Liu & Bobo Wing-Yee Mok & Bohao Chen & Pui Wang & Vincent Kwok-Man Poon & Hin Chu & Ch, 2022. "A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. Eva Stadler & Martin T. Burgess & Timothy E. Schlub & Shanchita R. Khan & Khai Li Chai & Zoe K. McQuilten & Erica M. Wood & Mark N. Polizzotto & Stephen J. Kent & Deborah Cromer & Miles P. Davenport &, 2023. "Monoclonal antibody levels and protection from COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    16. Ramon Roozendaal & Laura Solforosi & Daniel J. Stieh & Jan Serroyen & Roel Straetemans & Anna Dari & Muriel Boulton & Frank Wegmann & Sietske K. Rosendahl Huber & Joan E. M. van der Lubbe & Jenny Hend, 2021. "SARS-CoV-2 binding and neutralizing antibody levels after Ad26.COV2.S vaccination predict durable protection in rhesus macaques," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    17. Anna R. Mäkelä & Hasan Uğurlu & Liina Hannula & Ravi Kant & Petja Salminen & Riku Fagerlund & Sanna Mäki & Anu Haveri & Tomas Strandin & Lauri Kareinen & Jussi Hepojoki & Suvi Kuivanen & Lev Levanov &, 2023. "Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    18. Meng Wang & Adeline Dehlinger & Camila Fernández Zapata & Maya Golan & Gerardina Gallaccio & Leif E. Sander & Stephan Schlickeiser & Desiree Kunkel & Tanja Schmitz-Hübsch & Birgit Sawitzki & Arnon Kar, 2023. "Associations of myeloid cells with cellular and humoral responses following vaccinations in patients with neuroimmunological diseases," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    19. Yin-Feng Kang & Cong Sun & Jing Sun & Chu Xie & Zhen Zhuang & Hui-Qin Xu & Zheng Liu & Yi-Hao Liu & Sui Peng & Run-Yu Yuan & Jin-Cun Zhao & Mu-Sheng Zeng, 2022. "Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Jonas S. Heitmann & Claudia Tandler & Maddalena Marconato & Annika Nelde & Timorshah Habibzada & Susanne M. Rittig & Christian M. Tegeler & Yacine Maringer & Simon U. Jaeger & Monika Denk & Marion Ric, 2023. "Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31721-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.