Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Abstract

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.

Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

“…At 6 months post second dose, T cells secrete multiple cytokines and proliferate, indicating a broad range of memory function is retained by these cells. In addition, T cell responses are higher 6 months after vaccination in uninfected participants than they were in unvaccinated HCW 6 months after wave 1 infection in 2020, in a previous study of this cohort, (Tomic et al, 2022).…”

“…This difference had been significant for the BNT162b2 short and long interval groups 1 month after the second dose (Payne et al, 2021). Spike-specific T cell responses 6 months after vaccination were considerably greater in all groups than the historical median responses we observed using the same assay in this cohort pre-vaccination in 2020 (Tomic et al, 2022) six months after wave 1 infection (44 SFU/10 6, IQR 1-107).…”

“…(ii) The longitudinal cohort does not include never-vaccinated participants, because all the HCWs engaged with our studies across six sites took up vaccination. However, we have been able to compare responses six months after vaccination (in 2021) with historical data using the same assay in a subset of the same cohort in 2020, six months after wave 1 (ancestral strain) infection before vaccine were available (Tomic et al, 2022) and demonstrate that vaccine-induced responses in infection-naïve HCWs are higher than infection- induced responses. (iii) We were not able to perform all assays on all participants at all timepoints, due to lack of sample availability, missed follow up visits, and/or laboratory capacity.…”

“…Correlations with protection from infection at a population level have been observed for binding (Earle et al, 2021; Gilbert et al, 2022) and neutralising antibodies (Addetia et al; Feng et al, 2021; Gilbert et al, 2022; Khoury et al, 2021; Moore et al, 2021). The role of other, non-neutralising antibody functions, such as antibody-dependent NK cell activity, antibody-dependent phagocytosis or complement deposition, requires further investigation (Ewer et al, 2021; Kaplonek et al, 2022a; Tomic et al, 2022). However, monitoring of SARS- CoV-2 specific T cell immunity is also essential, as T cell defence is potentially a key explanation for lower case hospitalisation and mortality for omicron variant compared with earlier variants (Nyberg et al, 2022), despite omicron’s high mortality in unvaccinated populations (Mefsin et al, 2022).…”

Evaluation of QuantiFERON SARS-CoV-2 interferon-γ release assay following SARS-CoV-2 infection and vaccination

“…We and others have sought to characterise the immunological response to SARS-CoV-2 both following natural infection and vaccination (2–11). T cells are an important component of the immune response to SARS-CoV-2 infection and vaccination, persisting for several months post infection (4,8–10,12–16). T cells have also been extensively studied following vaccination alone (4,5,17–20) as well as in participants with combined past SARS-CoV-2 infection (5,17).…”