| Autor: |
Jean-Yves Blay, Cléa Melenotte, Fabrice Andre, Caroline Pradon, Agathe Carrier, Lydia Meziani, Guy Gorochov, Markus Maeurer, Carolina Alves Costa Silva, Safae Terrisse, Aurélien Marabelle, L. Cerbone, Eric De Sousa, Lisa Derosa, Joana R. Lérias, François-Xavier Danlos, Fanny Pommeret, Yacine Haddad, Florence Fenollar, Bertrand Gachot, Alice Bernard, Caroline Flament, Marianne Gazzano, Benoît Kloeckner, Florian Scotté, Anne-Gaëlle Goubet, Agathe Dubuisson, Cassandra Thelemaque, Eugenie Pizzato, Sophie Caillat-Zucman, Arthur Geraud, Fabrice Barlesi, Marine Mazzenga, Frank Griscelli, Mathieu F. Chevalier, Laurence Zitvogel, Bernard La Scola, Damien Drubay, Abdelhakim Ahmed-Belkacem, Pernelle Lavaud, Emeline Colomba, Jean-Eudes Fahrner, Gladys Ferrere, Eric Tartour, Pierre Ly, Marion Picard, Ariane Laparra, Jean-Philippe Spano, Makoto Miyara, Eric Deutsch, Mansouria Merad, Jean-Charles Soria, Imran Lahmar, Guido Kroemer, Emmanuelle Gallois |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.06.18.21258477 |
| Popis: |
Optimal vaccination and immunotherapy against coronavirus disease COVID-19 relies on the in-depth comprehension of immune responses determining the individual susceptibility to be infected by SARS-CoV-2 and to develop severe disease. We characterized the polarity and specificity of circulating SARS-CoV-2-specific T cell responses against whole virus lysates or 186 unique peptides derived from the SARS-CoV-2 or SARS-CoV-1 ORFeome on 296 cancer-bearing and 86 cancer-free individuals who were either from the pre-COVID-19 era (67 individuals) or contemporary COVID-19-free (237 individuals) or who developed COVID-19 (78 individuals) in 2020/21. The ratio between the prototypic T helper 1 (TH1) cytokine, interleukin-2, and the prototypic T helper 2 (TH2) cytokine, interleukin-5 (IL-5), released from SARS-CoV-2-specific memory T cells measured in early 2020, among SARS-CoV-2-negative persons, was associated with the susceptibility of these individuals to develop PCR-detectable SARS-CoV-2 infection in late 2020 or 2021. Of note, T cells from individuals who recovered after SARS-CoV-2 re-infection spontaneously produced elevated levels of IL-5 and secreted the immunosuppressive TH2 cytokine interleukin-10 in response to SARS-CoV-2 lysate, suggesting that TH2 responses to SARS-CoV-2 are inadequate. Moreover, individuals susceptible to SARS-CoV-2 infection exhibited a deficit in the TH1 peptide repertoire affecting the highly mutated receptor binding domain (RBD) amino acids (331-525) of the spike protein. Finally, current vaccines successfully triggered anti-RBD specific TH1 responses in 88% healthy subjects that were negative prior to immunization. These findings indicate that COVID-19 protection relies on TH1 cell immunity against SARS-CoV-2 S1-RBD which in turn likely drives the phylogenetic escape of the virus. The next generation of COVID-19 vaccines should elicit high-avidity TH1 (rather than TH2)-like T cell responses against the RBD domain of current and emerging viral variants. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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