Immunological imprinting: Understanding COVID-19

Abstract

Immunological imprinting generically refers to the effects prior exposures have on subsequent immune responses to, and eventually protection against, antigenically related viruses. Here, Koutsakos and Ellebedy explain different concepts and terms around imprinting and the fundamental immunological principles behind it. They also discuss the potential role imprinting may have in the context of COVID-19 vaccines.

Figure 1

Immunological and epidemiological patterns observed across populations with different exposure histories (A) Populations with different exposure histories may present with different antibody reactivity patterns toward antigenically related viruses. This immunological imprint can be observed in immunological data, like serological analyses. If these immunological differences translate into differences in susceptibility, the differential incidence of disease may be observed between populations over time. This “epidemiological imprint” can be observed in case distributions and is typically inferred from statistical models that link most likely exposure histories to the observed epidemiology. (B) Two commonly observed immunological patterns are antigenic seniority (observed in cross-sectional data) and back-boosting (observed in longitudinal data).

Figure 2

Determining the effects of prior exposures on subsequent immune responses (A) Inferring any negative effects of previous exposure on subsequent immune responses requires appropriate control groups. Observing greater antibodies toward antigen A than antigen B within an A→B group is not sufficient to conclude that prior exposure to A has a negative effect on subsequent response to B. (B) Differences in antibody titers alone are not sufficient to extrapolate a difference in protection from infection or severe disease. The effects of differential antibody titers will depend on their absolute values and the relationship between antibodies and protection.