Is universal coronavirus immunity possible?

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

T-cell immunity is essential 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 among immunocompromised (IP) patients. Pre-existing T-cell memory identifying SARS-CoV-2 antigens preceding COVID-19 vaccination or infection may be developed because of 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. However, 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 common human coronaviruses. Image Credit: kittipong053 / Shutterstock

About the study

In the present 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 did not 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 among related common Alpha- and beta-hCoVs in the same sample donor.

Furthermore, 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 at least 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 characterized the range of T-cell responses against hCoV by testing ex vivo reactivity using pepmixes derived from N, M, S1, and S2 antigens associated with endemic hCoVs. Additionally, the extent of responses against hCoVs in COVID-19-positive and -negative donors was assessed.   

Results

The study results showed that one of the subjects, a healthcare worker, 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 slightly detectable against the background, confirming the naive/unexposed status. Post-COVID-19 samples revealed a remarkable rise in reactivity against the four SARS-CoV-2 antigens prevalent in 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. Therefore, 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 overall SARS-CoV-2-specific CD4+ T-cell response against the eight assessed VOCs. Mean reductions of almost 27.8% against SARS-CoV-2 Beta, 16.2% against Gamma, and 22.5% against Epsilon VOCs were observed. Additionally, a reduction of 8.5% was noted against Alpha, 5.2% against Delta, and 0.83% against Kappa VOCs. However, the highest reduction of almost 47% was noted against the Omicron VOC.

On an individual level, the highest reduction of 33-fold was reported in one COVID-19-positive IP patient against the Omicron variant, and two other donors revealed a two-fold reduction. Notably, none of the donors displayed a reduction of over 10-fold  in 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 compared to 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 both COVID-19-positive and -negative donors displayed robust but highly inconsistent antigen-specific CD8+ responses. Overall, reactivity to a minimum of one antigen associated with each hCoV was observed among all the tested subjects. However, the simultaneous robust response against the four antigens related to each hCoV was remarkably more predominant among COVID-19-positive samples than in the -negative ones. 

Furthermore, considerably higher reactivity was observed against the S1 antigen of hCoVs NL63 and OC43 among COVID-19 survivors in comparison 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 significant association between COVID-19 responses and corresponding responses targeted against S2 and M of OC43 as well as N antigens of HKU1 and OC43. Overall, this indicated a potential 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 majority of the SARS-CoV-2 variants. However, 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 found in higher proportions among COVID-19 survivors than among unexposed individuals. The researchers believe that the present study supported the hypothesis that vaccines with broadly-specific anti-CoV T-cells could provide effective immunotherapies.  

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.