In a recent study posted to the bioRxiv* preprint server, researchers at Columbia University characterised reciprocal and non-reciprocal T-cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

T-cell immunity is crucial for positive clinical outcomes of SARS-CoV-2 infection. Hence, T-cell-focused cellular immunotherapy or vaccination might prove instrumental in enhancing coronavirus disease 2019 (COVID-19) protection amongst immunocompromised (IP) patients. Pre-existing T-cell memory identifying SARS-CoV-2 antigens preceding COVID-19 vaccination or infection could also be developed due to prior infections with endemic non-SARS human CoVs (hCoVs). Thus, SARS-CoV-2-primed T cells may detect emerging SARS-CoV-2 variants or other hCoV viruses and alter the course of following hCoV infections. Nonetheless, cross-immunity between SARS-CoV-2 and hCoVs needs extensive investigation. 

Study: The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and customary human coronaviruses. Image Credit: kittipong053 / Shutterstock

In regards to the study

In the current study, researchers explored the T-cell responses observed against the immunodominant SARS-CoV-2 and hCoV membrane (M), nucleocapsid (N), and spike (S) proteins.

The team assessed serial peripheral blood mononuclear cell (PBMC) samples obtained from healthy volunteers and immunocompromised individuals who did or didn’t report SARS-CoV-2 exposure to estimate T-cell responses against hCoVs like NL63, OC43, HKU1, and 229E, and SARS-CoV-2. Reactivity to associated immunodominant antigens was tested from amongst related common Alpha- and beta-hCoVs in the identical sample donor.

Moreover, the researchers determined whether previously acquired vaccination-induced or natural T-cell immunity cross-reacted against SARS-CoV-2 variants. This was achieved by obtaining PBMCs from COVID-19-positive and unexposed individuals vaccinated with not less than one SARS-CoV-2 vaccine. The resultant T-cells were further assessed for reactivity against eight SARS-CoV-2 variants of concern (VOCs). The team characterised the range of T-cell responses against hCoV by testing ex vivo reactivity using pepmixes derived from N, M, S1, and S2 antigens related to endemic hCoVs. Moreover, the extent of responses against hCoVs in COVID-19-positive and -negative donors was assessed.   

Results

The study results showed that one in all the topics, a healthcare employee, developed COVID-19 almost three months after collecting the initial sample. T-cell responses recorded at baseline against SARS-CoV-2 N, M, S1, and S2 antigens were barely detectable against the background, confirming the naive/unexposed status. Post-COVID-19 samples revealed a remarkable rise in reactivity against the 4 SARS-CoV-2 antigens prevalent within the CD4+ T cell compartment. The team noted maximal reactivity against the N protein antigen, followed by M, S2, and S1. The pattern and magnitude of reactivity against the non-SARS hCoV targets before and after COVID-19 stayed low and were negligibly impacted by COVID-19. Due to this fact, this particular sample donor had highly focused and robust antigen-specific T-cell memory against SARS-CoV-2 after infection.

The team noted that COVID-19-exposed donors largely maintained the general SARS-CoV-2-specific CD4+ T-cell response against the eight assessed VOCs. Mean reductions of just about 27.8% against SARS-CoV-2 Beta, 16.2% against Gamma, and 22.5% against Epsilon VOCs were observed. Moreover, a discount of 8.5% was noted against Alpha, 5.2% against Delta, and 0.83% against Kappa VOCs. Nonetheless, the very best reduction of just about 47% was noted against the Omicron VOC.

On a person level, the very best reduction of 33-fold was reported in a single COVID-19-positive IP patient against the Omicron variant, and two other donors revealed a two-fold reduction. Notably, not one of the donors displayed a discount of over 10-fold  within the extent of CD4+ T cell response against other variants. While three donors reported a two-fold reduction in reactivity against the Beta variant, some reported an over two-fold reduction against the Delta, Kappa, and Eta variants in comparison with the ancestral pool. Altogether, all tested COVID-19 survivors that displayed reactivity against the WT-peptide pool also exhibited the cross-recognition of other variants against Delta.

The team noted that each COVID-19-positive and -negative donors displayed robust but highly inconsistent antigen-specific CD8+ responses. Overall, reactivity to a minimum of 1 antigen related to each hCoV was observed amongst all of the tested subjects. Nonetheless, the simultaneous robust response against the 4 antigens related to every hCoV was remarkably more predominant amongst COVID-19-positive samples than within the -negative ones. 

Moreover, considerably higher reactivity was observed against the S1 antigen of hCoVs NL63 and OC43 amongst COVID-19 survivors as compared to SARS-CoV-2-negative individuals. Higher reactivity was also noted against S2 antigens of NL63 and HKU1, which rose further against S2 antigens of 229E and OC43. The team also found a big association between COVID-19 responses and corresponding responses targeted against S2 and M of OC43 in addition to N antigens of HKU1 and OC43. Overall, this indicated a possible association between T-cell immunity elicited after SARS-CoV-2 infection and reactivity directed against other hCoVs. This further suggested possible cross-reactivity and potential cross-protection.

Conclusion

The study findings highlighted broad T-cell immunity against the SARS-CoV-2 antigens observed in COVID-19 survivors. In vaccinated and in convalescent individuals, SARS-CoV-2 S-specific T-cells effectively detected the vast majority of the SARS-CoV-2 variants. Nonetheless, cross-reactivity against the SARS-CoV-2 Omicron variant was decreased by almost 50%. Responses against the N, S, and M antigens from the endemic hCoVs were present in higher proportions amongst COVID-19 survivors than amongst unexposed individuals. The researchers consider that the current study supported the hypothesis that vaccines with broadly-specific anti-CoV T-cells could provide effective immunotherapies.  

*Essential notice

bioRxiv publishes preliminary scientific reports that are usually not peer-reviewed and, due to this fact, shouldn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

• The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and customary human coronaviruses, Mithil K Soni, Edoardo Migliori, Jianing Fu, Amer Assal, Hei Ton Chan, Jian Pan, Prabesh Khatiwada, Rodica Ciubotariu, Michael S May, Marcus R Pereira, Valeria De Giorgi, Megan Sykes, Marcus Y Mapara, Pawel Muranski, bioRxiv 2023.01.03.519511, DOI: https://doi.org/10.1101/2023.01.03.519511, https://www.biorxiv.org/content/10.1101/2023.01.03.519511v1