The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

Abstract

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of “common cold”. In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and β-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

Comparative Study of T-Cell Repertoires after COVID-19 Immunization with Homologous or Heterologous Vaccine Booster

“…Hence, a possible explanation for the non-spike TCRs is the genetic homology between human coronaviruses (hCoVs) and the T-cell memory in common hCoV pathogens (OC43, HKU1, 229E, NL63). There are limited data on the sequencing and analysis of T-cell repertoires which are developed after COVID-19 immunization; however, the detection of non-spike-specific SARS-CoV-2 TCRβ rearrangements has also been reported in other studies [ 18 , 36 , 37 ]. Although there are no differences in the HOB and HEB groups regarding the percentage of COVID-19-related TCRs (spike TCRs: HOB 17.8% and HEB 17.1%; non-spike TCRs: HOB 82.2% and 82.9%), the numbers of these TCRs are significantly different between groups for spike (HOB 52.9 and HEB 90.2) and non-spike (HOB 245.4 and HEB 432.3).…”