tetano
Editor, Senior Moderator
Front Immunol
. 2024 Mar 28:15:1343716.
doi: 10.3389/fimmu.2024.1343716. eCollection 2024. High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients
Pierre-Gregoire Coulon[SUP] #[/SUP][SUP] 1 [/SUP], Swayam Prakash[SUP] #[/SUP][SUP] 1 [/SUP], Nisha R Dhanushkodi[SUP] 1 [/SUP], Ruchi Srivastava[SUP] 1 [/SUP], Latifa Zayou[SUP] 1 [/SUP], Delia F Tifrea[SUP] 2 [/SUP], Robert A Edwards[SUP] 2 [/SUP], Cesar J Figueroa[SUP] 3 [/SUP], Sebastian D Schubl[SUP] 3 [/SUP], Lanny Hsieh[SUP] 4 [/SUP], Anthony B Nesburn[SUP] 1 [/SUP], Baruch D Kuppermann[SUP] 1 [/SUP], Elmostafa Bahraoui[SUP] 5 [/SUP], Hawa Vahed[SUP] 6 [/SUP], Daniel Gil[SUP] 6 [/SUP], Trevor M Jones[SUP] 6 [/SUP], Jeffrey B Ulmer[SUP] 6 [/SUP], Lbachir BenMohamed[SUP] 1 5 6 7 [/SUP]
Affiliations
Background: Cross-reactive SARS-CoV-2-specific memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated.
Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms.
Results: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134[SUP]+[/SUP]CD137[SUP]+[/SUP]CD4[SUP]+[/SUP] and CD134[SUP]+[/SUP]CD137[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1[SUP]+[/SUP]TIM3[SUP]+[/SUP]TIGIT[SUP]+[/SUP]CTLA4[SUP]+[/SUP]CD4[SUP]+[/SUP] and PD-1[SUP]+[/SUP]TIM3[SUP]+[/SUP]TIGIT[SUP]+[/SUP]CTLA4[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells, detected both ex vivo and in vitro.
Conclusions: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.
Keywords: SARS-CoV-2; CD4 + T cells; CD8 + T cells; COVID-19; asymptomatic; common cold coronavirus; exhaustion α-CCCs/SARS-CoV-2 cross-reactive T cells in asymptomatic COVID-19 infection; symptomatic.
. 2024 Mar 28:15:1343716.
doi: 10.3389/fimmu.2024.1343716. eCollection 2024. High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients
Pierre-Gregoire Coulon[SUP] #[/SUP][SUP] 1 [/SUP], Swayam Prakash[SUP] #[/SUP][SUP] 1 [/SUP], Nisha R Dhanushkodi[SUP] 1 [/SUP], Ruchi Srivastava[SUP] 1 [/SUP], Latifa Zayou[SUP] 1 [/SUP], Delia F Tifrea[SUP] 2 [/SUP], Robert A Edwards[SUP] 2 [/SUP], Cesar J Figueroa[SUP] 3 [/SUP], Sebastian D Schubl[SUP] 3 [/SUP], Lanny Hsieh[SUP] 4 [/SUP], Anthony B Nesburn[SUP] 1 [/SUP], Baruch D Kuppermann[SUP] 1 [/SUP], Elmostafa Bahraoui[SUP] 5 [/SUP], Hawa Vahed[SUP] 6 [/SUP], Daniel Gil[SUP] 6 [/SUP], Trevor M Jones[SUP] 6 [/SUP], Jeffrey B Ulmer[SUP] 6 [/SUP], Lbachir BenMohamed[SUP] 1 5 6 7 [/SUP]
Affiliations
- PMID: 38605956
- PMCID: PMC11007208
- DOI: 10.3389/fimmu.2024.1343716
Background: Cross-reactive SARS-CoV-2-specific memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated.
Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms.
Results: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134[SUP]+[/SUP]CD137[SUP]+[/SUP]CD4[SUP]+[/SUP] and CD134[SUP]+[/SUP]CD137[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1[SUP]+[/SUP]TIM3[SUP]+[/SUP]TIGIT[SUP]+[/SUP]CTLA4[SUP]+[/SUP]CD4[SUP]+[/SUP] and PD-1[SUP]+[/SUP]TIM3[SUP]+[/SUP]TIGIT[SUP]+[/SUP]CTLA4[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells, detected both ex vivo and in vitro.
Conclusions: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.
Keywords: SARS-CoV-2; CD4 + T cells; CD8 + T cells; COVID-19; asymptomatic; common cold coronavirus; exhaustion α-CCCs/SARS-CoV-2 cross-reactive T cells in asymptomatic COVID-19 infection; symptomatic.