1. The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals
- Author
-
Jean-Eudes, Fahrner, Imran, Lahmar, Anne-Gaëlle, Goubet, Yacine, Haddad, Agathe, Carrier, Marine, Mazzenga, Damien, Drubay, Carolina, Alves Costa Silva, Eric, de Sousa, Cassandra, Thelemaque, Cléa, Melenotte, Agathe, Dubuisson, Arthur, Geraud, Gladys, Ferrere, Roxanne, Birebent, Camille, Bigenwald, Marion, Picard, Luigi, Cerbone, Joana R, Lérias, Ariane, Laparra, Alice, Bernard-Tessier, Benoît, Kloeckner, Marianne, Gazzano, François-Xavier, Danlos, Safae, Terrisse, Eugenie, Pizzato, Caroline, Flament, Pierre, Ly, Eric, Tartour, Nadine, Benhamouda, Lydia, Meziani, Abdelhakim, Ahmed-Belkacem, Makoto, Miyara, Guy, Gorochov, Fabrice, Barlesi, Alexandre, Trubert, Benjamin, Ungar, Yeriel, Estrada, Caroline, Pradon, Emmanuelle, Gallois, Fanny, Pommeret, Emeline, Colomba, Pernelle, Lavaud, Marc, Deloger, Nathalie, Droin, Eric, Deutsch, Bertrand, Gachot, Jean-Philippe, Spano, Mansouria, Merad, Florian, Scotté, Aurélien, Marabelle, Frank, Griscelli, Jean-Yves, Blay, Jean-Charles, Soria, Miriam, Merad, Fabrice, André, Juliette, Villemonteix, Mathieu F, Chevalier, Sophie, Caillat-Zucman, Florence, Fenollar, Emma, Guttman-Yassky, Odile, Launay, Guido, Kroemer, Bernard, La Scola, Markus, Maeurer, Lisa, Derosa, Laurence, Zitvogel, Université Paris-Saclay, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), AP-HP. Université Paris Saclay, Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), and Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
- Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,SARS-CoV-2 ,T-Lymphocytes ,COVID-19 ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Antibodies, Neutralizing ,Antiviral Restriction Factors ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Oncology ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Neoplasms ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Spike Glycoprotein, Coronavirus ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology - Abstract
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. Significance: 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. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873
- Published
- 2021
- Full Text
- View/download PDF