Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Abstract

Vaccination against SARS-CoV-2 results in protection from acquisition of infection as well as improved clinical outcomes even if infection occurs, likely reflecting a combination of residual vaccine-elicited immunity and the recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and T cell immunity after vaccination of seropositive individuals, and after breakthrough infection in vaccinated individuals. Intensive and early longitudinal sampling reveals the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titres. In breakthrough infections, the delayed kinetics of humoral immune recall provides a mechanism for the lack of early control of viral replication but likely underpins accelerated viral clearance and the protective effects of vaccination against severe COVID-19.

Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast?

“…Studies of passive antibody administration (primarily in unvaccinated individuals) suggest that high (monoclonal) antibody levels delivered in the first week after symptom onset can play a significant role in reducing the progression to severe infection and can accelerate viral clearance (Box 2). A rapid rise in nAb responses after breakthrough infection in vaccinated individuals has been shown in this time window, suggesting that B cell recall and nAb production may play a similar role in reducing the severity of infection 57,58 . An analysis of the dynamics of immune recall early after breakthrough SARS-CoV-2 infection in the Delta-dominant era shows rapid recall of antibody responses occurring around day 5 after symptom onset (around day 8 after infection), but weak or no recall of CD4 + T cell and CD8 + T cell responses in blood around the same time 58 (Fig.…”

“…A rapid rise in nAb responses after breakthrough infection in vaccinated individuals has been shown in this time window, suggesting that B cell recall and nAb production may play a similar role in reducing the severity of infection 57,58 . An analysis of the dynamics of immune recall early after breakthrough SARS-CoV-2 infection in the Delta-dominant era shows rapid recall of antibody responses occurring around day 5 after symptom onset (around day 8 after infection), but weak or no recall of CD4 + T cell and CD8 + T cell responses in blood around the same time 58 (Fig. 3b-d).…”

Instructing durable humoral immunity for COVID-19 and other vaccinable diseases

“…Moreover, prior studies in other systems have shown that memory B cells have improved breadth and diversity relative to serum antibodies contemporaneously produced by long-lived plasma cells, increasing the chances that they can recognize viruses despite escape mutations (Purtha et al, 2011). Upon recognition, antibody recall responses to SARS-CoV-2 tend to begin at least several days before primary responses (Koutsakos et al, 2021), thereby at least theoretically increasing the chances that infections can be terminated even before symptom onset. Yet as SARS-CoV-2 has evolved, the incubation period, which is the time between infection and symptom onset, has shortened (Kang et al, 2021).…”

Eleven‐month longitudinal study of antibodies in SARS‐CoV‐2 exposed and naïve primary health care workers upon COVID‐19 vaccination

“…In addition to symptomatic cases, seroconversion of N FL antibodies (including IgM) was indicative of asymptomatic infections that appeared to increase further at the later timepoints (T8) when the lowest levels of IgG were attained. Although advances are underway to establish correlates of protection [3,[26][27][28][29][30], not having them also makes it more difficult to link analysis of antibody waning with effectiveness [31], and to predict the impact of VoC like Omicron. In prior studies, 1 month after the second dose of Moderna, 85% of participants had neutralizing activity against Omicron but after 7 months this was reduced to 55% [32].…”