Fig. 2. Protection from acquisition of SARS-CoV-2 infection tracks the neutralizing antibody responses.

From comparison of situations where neutralizing antibody (nAb) and memory T cell responses are decoupled, protection appears to be predicted by the level of nAbs. a | The nAb levels, circulating spike-specific (AIM⁺) CD4⁺ T cell levels and AIM⁺CD8⁺ T cell levels, and protection against symptomatic infection for the Beta variant versus the ancestral SARS-CoV-2 strain. nAb titres (measured as the 50% focus-reduction neutralizing antibody titre (FRNT50)) are reduced 3.9-fold, 8.8-fold and at least 10-fold for the Delta (B.1.167.2), Beta (B.1.351) and Omicron (B.1.1.529) variants, respectively^24,63. By contrast, T cell responses to the variants are largely preserved, including to the Beta, Delta and Omicron variants^37–39,65. Protection decreases as expected from the reduced nAb level^24,41. b | Vaccination of previously infected individuals leads to higher peak nAb levels than seen in vaccination of naive individuals⁴⁴. However, peak CD4⁺ T cell and CD8⁺ T cell responses are similar following vaccination of previously infected individuals and naive individuals⁴⁵. The effectiveness after BNT162b2 vaccination in recovered individuals (recovered from infection with the Delta variant) is significantly higher than the effectiveness after vaccination in naive individuals (93% versus 85%, P = 0.006), tracking the increased nAb responses⁴⁹. c | The observed waning of nAb responses (data obtained from refs^50,51,80) has led to the suggestion that the relative contribution of T cell-mediated immunity to protection may increase over time. However, the decay rate of antigen-specific T cells in the circulation is similar to that observed for nAb titres⁴⁵. Although protection wanes with time⁷, it is not possible to differentiate the contribution of humoral or T cell responses, as they decay at similar rates.