Adaptive immunity to human coronaviruses is widespread but low in magnitude

Abstract

Objectives. Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults. Methods. We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals. Antigen-specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation-induced marker assay and characterised for memory phenotype and chemokine receptor expression. Results. T-cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6 + central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung-draining lymph nodes. Conclusion. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.

Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

“…Previous work has suggested that substantial immune memory involving both arms of adaptive immune memory is generated against CCC 17,23,25,26 . We observed that about 72-81% of subjects exhibited immune CD4+ T cell memory responses to each of the 4 CCC studied, consistent with frequencies detected in both community and heath care works cohorts 26 , and similar to the findings of Tan et al 25 . Remarkably, we found a stable and sustained T cell and antibody response against CCC which are supported by recent experimental findings from Cohen et al 41 or mathematical modeling 19,20 and argues against the short-lived nature of CCC responses [16][17][18] .…”

“…Previous work has suggested that substantial immune memory involving both arms of adaptive immune memory is generated against CCC 17,23,25,26 . We observed that about 72-81% of subjects exhibited immune CD4+ T cell memory responses to each of the 4 CCC studied, consistent with frequencies detected in both community and heath care works cohorts 26 , and similar to the findings of Tan et al 25 .…”

“…Some discrepancies may be reconciled as some reports consider immunity as protection from re-infection while others consider protection from symptomatic disease. CCC infections are associated with generation of antibody titers widely detectable in the human population 17,[23][24][25] . However, little data is available regarding the frequency of memory T cell responses against CCC, and in particular their stability overtime.…”

“…Furthermore, it has been widely reported that CCC T cell responses are associated with some degree of cross-reactivity with SARS-CoV-2, and that this cross-reactivity can at least in part explain the pre-existing T cell memory reactivity recognizing SARS-CoV-2 sequences, observed in SARS-CoV-2 unexposed subjects 25–29 . A putative role for CCC cross-reactive T cells in modulating COVID-19 vaccination and disease outcomes has been indicated by several independent studies 26,30–33 .…”

“…Understanding the steady state dynamics of CCC antibody and T cell responses in humans is of potential relevance in the context of the long-term evolution of the SARS-CoV-2 pandemic, in the context of the current scenario, where a large fraction of the human population is exposed and/or vaccinated. Furthermore, it has been widely reported that CCC T cell responses are associated with some degree of cross-reactivity with SARS-CoV-2, and that this cross-reactivity can at least in part explain the pre-existing T cell memory reactivity recognizing SARS-CoV-2 sequences, observed in SARS-CoV-2 unexposed subjects [25][26][27][28][29] . A putative role for CCC cross-reactive T cells in modulating COVID-19 vaccination and disease outcomes has been indicated by several independent studies 26,[30][31][32][33] .…”