Studying the Imprinting Effect in Cohort Studies of Covid Vaccines

Immune imprinting denotes a phenomenon where previous exposure to a viral antigen, through infection or vaccination, imprints that antigen in immunological memory. When the immune system is exposed to a new strain or a new variant, part of the response targets the historical antigen(s), and the fight against the new offender is less effective. It was recently argued that observational studies that show evidence of immune imprinting by prior vaccination reflect colliding (selection) bias, not imprinting. The collider is a first infection, and the two causes are vaccination and susceptibility to infection. As will be explained, the claim is not uniformly valid, nor can it be verified or refuted based on a construct called susceptibility. Moreover, if the bias is significant at all, underestimation of the true effect of immune imprinting is equally possible.