Contributors: Laboratoire de Virologie [Strasbourg]; Immuno-Rhumatologie Moléculaire; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM); Virus et Immunité - Virus and immunity; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC); Vaccine Research Institute (VRI); Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); Les Hôpitaux Universitaires de Strasbourg (HUS); Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Hôpital Henri Mondor; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); Institut Mondor de Recherche Biomédicale (IMRB); Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); CHU Strasbourg; This work was supported by the Strasbourg University Hospital (SeroCoV-HUS; PRI 7782), ANR-18-CE17-0028, ANR-11-LABX-0070_TRANSPLANTEX, Strasbourg University and the Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). Work in OS lab is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. DP is supported by the Vaccine Research Institute.; We are grateful to the participants of the study. We thank Dr. Negar Sedghi and Dr. Dominique Desprez for reporting us the breakthrough cases.; ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020); ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010); Virus et Immunité - Virus and immunity (CNRS-UMR3569); Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Vaccine Research Institute [Créteil, France] (VRI); Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
نبذة مختصرة : BackgroundSARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized.MethodsWe analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally.ResultsThe first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4+IL-2+ cells) and CD8 effector response (CD8+IFNγ+ cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection.ConclusionsAn analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies.
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