Data from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

  1. Jean-Eudes Fahrner
  2. Imran Lahmar
  3. Anne-Gaëlle Goubet
  4. Yacine Haddad
  5. Agathe Carrier
  6. Marine Mazzenga
  7. Damien Drubay
  8. Carolina Alves Costa Silva
  9. Eric de Sousa
  10. Cassandra Thelemaque
  11. Cléa Melenotte
  12. Agathe Dubuisson
  13. Arthur Geraud
  14. Gladys Ferrere
  15. Roxanne Birebent
  16. Camille Bigenwald
  17. Marion Picard
  18. Luigi Cerbone
  19. Joana R. Lérias
  20. Ariane Laparra
  21. Alice Bernard-Tessier
  22. Benoît Kloeckner
  23. Marianne Gazzano
  24. François-Xavier Danlos
  25. Safae Terrisse
  26. Eugenie Pizzato
  27. Caroline Flament
  28. Pierre Ly
  29. Eric Tartour
  30. Nadine Benhamouda
  31. Lydia Meziani
  32. Abdelhakim Ahmed-Belkacem
  33. Makoto Miyara
  34. Guy Gorochov
  35. Fabrice Barlesi
  36. Alexandre Trubert
  37. Benjamin Ungar
  38. Yeriel Estrada
  39. Caroline Pradon
  40. Emmanuelle Gallois
  41. Fanny Pommeret
  42. Emeline Colomba
  43. Pernelle Lavaud
  44. Marc Deloger
  45. Nathalie Droin
  46. Eric Deutsch
  47. Bertrand Gachot
  48. Jean-Philippe Spano
  49. Mansouria Merad
  50. Florian Scotté
  51. Aurélien Marabelle
  52. Frank Griscelli
  53. Jean-Yves Blay
  54. Jean-Charles Soria
  55. Miriam Merad
  56. Fabrice André
  57. Juliette Villemonteix
  58. Mathieu F. Chevalier
  59. Sophie Caillat-Zucman
  60. Florence Fenollar
  61. Emma Guttman-Yassky
  62. Odile Launay
  63. Guido Kroemer
  64. Bernard La Scola
  65. Markus Maeurer
  66. Lisa Derosa
  67. Laurence Zitvogel

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

<div>Abstract<p>Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants.</p>Significance:<p>This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike.</p><p><i>See related commentary by McGary and Vardhana, p. 892</i>.</p><p><i>This article is highlighted in the In This Issue feature, p. 873</i></p></div>

Article activity feed

  1. Version published to 10.1158/2159-8290.c.6549506.v1
  2. Version published to 10.1158/2159-8290.22540916.v1
  3. Version published to 10.1158/2159-8290.22540916
  4. Version published to 10.1158/2159-8290.c.6549506
  5. Version published to 10.1158/2159-8290.22540913
  6. Version published to 10.1158/2159-8290.22540913.v1
  7. Version published to 10.1158/2159-8290.cd-21-1441
  8. ScreenIT

    SciScore for 10.1101/2021.06.18.21258477: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Material and methods: Patient and cohort characteristics: All clinical studies were conducted after written informed consent in accordance with Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki.
    IRB: Protocol approval was obtained from an independent ethics committee (ethics protocol number EudraCT No: 2020-001250-21).
    IACUC: We obtained approval from the local ethical committee and the French ministry of research (DC-2008-64) for handling and conservation of these samples.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationContamination: All cells and antigens were tested negative for Mycoplasma before use.

    Table 2: Resources

    Antibodies
    SentencesResources
    Finally, specific antibodies of patients are detected with anti-IgG or -IgA or -IgM secondary antibodies.
    anti-IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 IHUMI2, IHUMI845, IHUMI846, IHUMI847 (early 2020 episode), IHUMI2096 (20A.EU2, B.1.160) and IHUMI2514 (20C, B.1.367) [80] IHUMI3076 (20I/501Y.V1, B.1.1.7), IHUMI3147 (20H/501Y.V2, B.1.351) and IHUMI3191 (20J/501Y.V3, P.1) strains were isolated from human nasopharyngeal swab as previously described [35] and grown in Vero E6 cells (ATCC CRL-1586) in Minimum Essential Medium culture medium (MEM) with 4% fetal calf serum (FCS) and 1% L-glutamine.
    Vero E6
    suggested: None
    Influenza strains H1N1 (0022641132) and H3N2 (8091056304) were isolated then produced from human nasopharyngeal swab in MDCK cells (ATCC CCL-34) in MEM with 10% FCS and 1% L-glutamine.
    MDCK
    suggested: None
    Coronavirus OC43 (ATCC vr-1558) was grown in HCT8 cells (ATCC CCL-244) in RPMI with 10% FCS.
    HCT8
    suggested: None
    Software and Algorithms
    SentencesResources
    Human biological samples and associated data were obtained from NeuroBioTec (CRB HCL, Lyon France, Biobank BB-0033-00046) and Virginie Pitiot.
    NeuroBioTec
    suggested: (NeuroBioTec, RRID:SCR_013842)
    SARS-CoV-2 RNA was detected using one of two available techniques at Gustave Roussy: the GeneFinder COVID-19 Plus RealAmp kit (ELITech Group) targeting three regions (RdRp gene, nucleocapsid and envelope genes) on the ELITe InGenius (ELITech Group) or the multiplex real-time RT-PCR diagnostic kit (the Applied Biosystems TaqPath COVID-19
    GeneFinder
    suggested: (GENEFINDER, RRID:SCR_009190)
    HEPES Buffer Solution (catalog reference: 15630-056), MEM NEAA (catalog reference: 1140-035) from GIBCO/ThermoFisher Scientific and Recombinant Human IL-2 (PHAR000306) from Gustave Roussy Institute pharmacy.
    GIBCO/ThermoFisher
    suggested: None
    Acquisitions and analyses were performed on CytoFLEX S purchased from Beckman Coulter (catalog reference: B75442)/FACSAria Fusion purchased from BDbiosciences and FlowJo Software from Treestar respectively.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    The peptides from the ORF8 and ORF10 proteins were selected by dividing the sequences of the SARS-CoV-2 ORF8 protein (RefSeq ID QHD43422.1) and of the ORF10 protein (RefSeq ID QHI42199.1) in overlapping 15 amino acid segments.
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04341207RecruitingEpidemiology of SARS-CoV-2 and Mortality to Covid19 Disease …
    NCT04341142RecruitingAssessment of Serological Techniques for Screening Patients …
    NCT01159288CompletedTrial of a Vaccination With Tumor Antigen-loaded Dendritic C…
    NCT02528357CompletedGSK3174998 Alone and With Pembrolizumab in Participants With…
    NCT03334617RecruitingPhase II Umbrella Study of Novel Anti-cancer Agents in Patie…
    NCT02423863CompletedIn Situ, Autologous Therapeutic Vaccination Against Solid Ca…
    NCT03818685RecruitingEvaluate the Clinical Benefit of a Post-operative Treatment …

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  9. Version published to 10.1101/2021.06.18.21258477v1 on medRxiv