TY - JOUR
T1 - The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals
AU - Lyon COVID Study Group
AU - Fahrner, Jean Eudes
AU - Lahmar, Imran
AU - Goubet, Anne Gaelle
AU - Haddad, Yacine
AU - Carrier, Agathe
AU - Mazzenga, Marine
AU - Drubay, Damien
AU - Costa Silva, Carolina Alves
AU - De Sousa, Eric
AU - Thelemaque, Cassandra
AU - Melenotte, Clea
AU - Dubuisson, Agathe
AU - Geraud, Arthur
AU - Ferrere, Gladys
AU - Birebent, Roxanne
AU - Bigenwald, Camille
AU - Picard, Marion
AU - Cerbone, Luigi
AU - Lerias, Joana R.
AU - Laparra, Ariane
AU - Bernard-Tessier, Alice
AU - Kloeckner, Benoit
AU - Gazzano, Marianne
AU - Danlos, Francois Xavier
AU - Terrisse, Safae
AU - Pizzato, Eugenie
AU - Flament, Caroline
AU - Ly, Pierre
AU - Tartour, Eric
AU - Benhamouda, Nadine
AU - Meziani, Lydia
AU - Ahmed-Belkacem, Abdelhakim
AU - Miyara, Makoto
AU - Gorochov, Guy
AU - Barlesi, Fabrice
AU - Trubert, Alexandre
AU - Ungar, Benjamin
AU - Estrada, Yeriel
AU - Pradon, Caroline
AU - Gallois, Emmanuelle
AU - Pommeret, Fanny
AU - Colomba, Emeline
AU - Deloger, Marc
AU - Droin, Nathalie
AU - Deutsch, Eric
AU - Scotte, Florian
AU - Marabelle, Aurelien
AU - Andre, Fabrice
AU - Kroemer, Guido
AU - Zitvogel, Laurence
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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 vaccineinduced 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.
AB - 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 vaccineinduced 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.
KW - Complementizer
KW - Eoliano (i.e. Italian dialect spoken in the Eolian islands)
KW - Finite complementation
KW - Left periphery
KW - Syncretic C-system
UR - http://www.scopus.com/inward/record.url?scp=85128161114&partnerID=8YFLogxK
U2 - 10.1158/2159-8290.CD-21-1441
DO - 10.1158/2159-8290.CD-21-1441
M3 - Article
C2 - 35179201
AN - SCOPUS:85128161114
SN - 2159-8274
VL - 12
SP - 958
EP - 983
JO - Cancer Discovery
JF - Cancer Discovery
IS - 4
ER -