tetano
Editor, Senior Moderator
J Virol
. 2022 Jun 14;e0050922.
doi: 10.1128/jvi.00509-22. Online ahead of print.
Longitudinal Assessment of SARS-CoV-2-Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multicytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity
Jonah Lin[SUP] #[/SUP][SUP] 1 [/SUP], Ryan Law[SUP] #[/SUP][SUP] 1 [/SUP], Chapin S Korosec[SUP] #[/SUP][SUP] 2 [/SUP], Christine Zhou[SUP] #[/SUP][SUP] 1 [/SUP], Wan Hon Koh[SUP] 1 3 [/SUP], Mohammad Sajjad Ghaemi[SUP] 4 [/SUP], Philip Samaan[SUP] 3 5 [/SUP], Hsu Kiang Ooi[SUP] 4 [/SUP], Vitaliy Matveev[SUP] 3 [/SUP], FengYun Yue[SUP] 3 [/SUP], Anne-Claude Gingras[SUP] 6 7 [/SUP], Antonio Estacio[SUP] 8 [/SUP], Megan Buchholz[SUP] 9 [/SUP], Patti Lou Cheatley[SUP] 9 [/SUP], Avid Mohammadi[SUP] 3 [/SUP], Rupert Kaul[SUP] 3 [/SUP], Katerina Pavinski[SUP] 10 [/SUP], Samira Mubareka[SUP] 11 [/SUP], Allison J McGeer[SUP] 6 [/SUP], Jerome A Leis[SUP] 11 [/SUP], Jane M Heffernan[SUP] 2 [/SUP], Mario Ostrowski[SUP] 1 3 12 8 5 [/SUP]
Affiliations
Abstract
Cell-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected survivors over a 1-year post-symptom onset (PSO) interval by ex vivo cytokine enzyme-linked immunosorbent spot assay (ELISpot) assay. All subjects demonstrated SARS-CoV-2-specific gamma interferon (IFN-γ), interleukin 2 (IL-2), and granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4[SUP]+[/SUP] T cells, targeted all structural proteins (nucleocapsid, membrane, and spike) except envelope, with GzmB and IL-2 greater than IFN-γ. Mathematical modeling predicted that (i) cytokine responses peaked at 6 days for IFN-γ, 36 days for IL-2, and 7 days for GzmB, (ii) severe illness was associated with reduced IFN-γ and GzmB but increased IL-2 production rates, and (iii) males displayed greater production of IFN-γ, whereas females produced more GzmB. Ex vivo responses declined over time, with persistence of IL-2 in 86% and of IFN-γ and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modeled to be 139 days (~4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the nucleocapsid and membrane regions. Both SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell clones were able to kill target cells, though CD8 tended to be more potent. IMPORTANCE Our findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control and shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and they indicate robust persistence of T cell memory at least 1 year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.
Keywords: ELISpot assay; SARS-CoV-2; T cell immunity; cytokines; granzyme B; immune modeling.
. 2022 Jun 14;e0050922.
doi: 10.1128/jvi.00509-22. Online ahead of print.
Longitudinal Assessment of SARS-CoV-2-Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multicytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity
Jonah Lin[SUP] #[/SUP][SUP] 1 [/SUP], Ryan Law[SUP] #[/SUP][SUP] 1 [/SUP], Chapin S Korosec[SUP] #[/SUP][SUP] 2 [/SUP], Christine Zhou[SUP] #[/SUP][SUP] 1 [/SUP], Wan Hon Koh[SUP] 1 3 [/SUP], Mohammad Sajjad Ghaemi[SUP] 4 [/SUP], Philip Samaan[SUP] 3 5 [/SUP], Hsu Kiang Ooi[SUP] 4 [/SUP], Vitaliy Matveev[SUP] 3 [/SUP], FengYun Yue[SUP] 3 [/SUP], Anne-Claude Gingras[SUP] 6 7 [/SUP], Antonio Estacio[SUP] 8 [/SUP], Megan Buchholz[SUP] 9 [/SUP], Patti Lou Cheatley[SUP] 9 [/SUP], Avid Mohammadi[SUP] 3 [/SUP], Rupert Kaul[SUP] 3 [/SUP], Katerina Pavinski[SUP] 10 [/SUP], Samira Mubareka[SUP] 11 [/SUP], Allison J McGeer[SUP] 6 [/SUP], Jerome A Leis[SUP] 11 [/SUP], Jane M Heffernan[SUP] 2 [/SUP], Mario Ostrowski[SUP] 1 3 12 8 5 [/SUP]
Affiliations
- PMID: 35699447
- DOI: 10.1128/jvi.00509-22
Abstract
Cell-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected survivors over a 1-year post-symptom onset (PSO) interval by ex vivo cytokine enzyme-linked immunosorbent spot assay (ELISpot) assay. All subjects demonstrated SARS-CoV-2-specific gamma interferon (IFN-γ), interleukin 2 (IL-2), and granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4[SUP]+[/SUP] T cells, targeted all structural proteins (nucleocapsid, membrane, and spike) except envelope, with GzmB and IL-2 greater than IFN-γ. Mathematical modeling predicted that (i) cytokine responses peaked at 6 days for IFN-γ, 36 days for IL-2, and 7 days for GzmB, (ii) severe illness was associated with reduced IFN-γ and GzmB but increased IL-2 production rates, and (iii) males displayed greater production of IFN-γ, whereas females produced more GzmB. Ex vivo responses declined over time, with persistence of IL-2 in 86% and of IFN-γ and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modeled to be 139 days (~4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the nucleocapsid and membrane regions. Both SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell clones were able to kill target cells, though CD8 tended to be more potent. IMPORTANCE Our findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control and shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and they indicate robust persistence of T cell memory at least 1 year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.
Keywords: ELISpot assay; SARS-CoV-2; T cell immunity; cytokines; granzyme B; immune modeling.