Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19

Long-term immunity to SARS-CoV-2 is crucial for the development of herd immunity and the aim of vaccination approaches. Reports on rapidly decreasing antibody titers question the efficacy of humoral immunity. The relevance of T cell memory after COVID-19 is yet unclear. Longitudinal analysis of SARS-CoV-2 immunity in convalescents up to six months post-infection revealed decreasing and stable spike and nucleocapsid antibody responses, respectively. In contrast, T cell responses remained robust and even increased in frequency and intensity. Single epitope mapping of T cell diversity over time identified ORF-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses and may be fundamental for vaccine design.

[1]  Leo Swadling,et al.  T cells in COVID-19 — united in diversity , 2020, Nature Immunology.

[2]  P. Sopp,et al.  Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19 , 2020, Nature Immunology.

[3]  V. Shinde,et al.  Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine , 2020, The New England journal of medicine.

[4]  M. Marshall.  The lasting misery of coronavirus long-haulers , 2020, Nature.

[5]  P. Doherty,et al.  Suboptimal SARS-CoV-2−specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype , 2020, Proceedings of the National Academy of Sciences.

[6]  M. Dake,et al.  Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure , 2020, medRxiv.

[7]  L. Carter,et al.  Functional SARS-CoV-2-specific immune memory persists after mild COVID-19 , 2020, medRxiv.

[8]  Leora I. Horwitz,et al.  Post-discharge health status and symptoms in patients with severe COVID-19 , 2020, medRxiv.

[9]  A. Rimmer.  Covid-19: Impact of long term symptoms will be profound, warns BMA , 2020, BMJ.

[10]  Xinghua Tan,et al.  Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs , 2020, Cell Death Discovery.

[11]  S. Mallal,et al.  Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans , 2020, Science.

[12]  J. Dowds,et al.  Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection , 2020, medRxiv.

[13]  Zeyu Chen,et al.  T cell responses in patients with COVID-19 , 2020, Nature Reviews Immunology.

[14]  U. Reimer,et al.  SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19 , 2020, Nature.

[15]  Eike Nagel,et al.  Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) , 2020, JAMA cardiology.

[16]  Otto O. Yang,et al.  Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19 , 2020, The New England journal of medicine.

[17]  Martin Linster,et al.  SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls , 2020, Nature.

[18]  J. Mascola,et al.  An mRNA Vaccine against SARS-CoV-2 — Preliminary Report , 2020, The New England journal of medicine.

[19]  Angelo Carfì,et al.  Persistent Symptoms in Patients After Acute COVID-19. , 2020, JAMA.

[20]  T. Segura,et al.  Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description , 2020, Brain : a journal of neurology.

[21]  Shu-Min Lin,et al.  Relative COVID-19 Viral Persistence and Antibody Kinetics , 2020, medRxiv.

[22]  Morten Nielsen,et al.  Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19 , 2020, Cell.

[23]  A. Sette,et al.  Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome , 2020, Science Immunology.

[24]  X. Tang,et al.  Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections , 2020, Nature Medicine.

[25]  L. Gieselmann,et al.  Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients , 2020, Cell.

[26]  K. Khunti,et al.  New-Onset Diabetes in Covid-19 , 2020, The New England journal of medicine.

[27]  Jérémie F. Cohen,et al.  Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study , 2020, BMJ.

[28]  Linqi Zhang,et al.  Human neutralizing antibodies elicited by SARS-CoV-2 infection , 2020, Nature.

[29]  J. Greenbaum,et al.  Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals , 2020, Cell.

[30]  Nan Wu,et al.  Persistent viral RNA positivity during the recovery period of a patient with SARS‐CoV‐2 infection , 2020, Journal of medical virology.

[31]  Marta Elena Losa-Iglesias,et al.  Footwear used by older people and a history of hyperkeratotic lesions on the foot , 2017, Medicine.

[32]  R. Baric,et al.  Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses , 2016, Immunity.

[33]  A. Bertoletti,et al.  Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection , 2016, Vaccine.

[34]  M. Ravid,et al.  A Six-Year Follow-up Study , 2016 .

[35]  Jincun Zhao,et al.  Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection , 2014, Journal of Virology.

[36]  E. Rosenberg,et al.  HIV-Specific Cytolytic CD4 T Cell Responses During Acute HIV Infection Predict Disease Outcome , 2012, Science Translational Medicine.

[37]  Hong Yang,et al.  Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study , 2011, The Journal of Immunology.

[38]  Jincun Zhao,et al.  T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice , 2010, Journal of Virology.

[39]  Taeg S. Kim,et al.  Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection , 2010, The Journal of experimental medicine.

[40]  Mushtaq Ahmed,et al.  Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus , 2008, The Journal of experimental medicine.

[41]  W. Cao,et al.  Disappearance of antibodies to SARS-associated coronavirus after recovery. , 2007, The New England journal of medicine.

[42]  T. Storni,et al.  Innate Immunity Together with Duration of Antigen Persistence Regulate Effector T Cell Induction , 2003, The Journal of Immunology.

[43]  D. Chaplin,et al.  Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin , 2000, European journal of immunology.

[44]  David Gray,et al.  Immunological Memory and Protective Immunity: Understanding Their Relation , 1996, Science.