Immune imprinting and SARS-CoV-2 vaccine design

Abstract

Reformulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines with variant strains is being pursued to combat the global surge in infections. We hypothesize that this may be suboptimal due to immune imprinting from earlier vaccination or infection with the original SARS-CoV-2 strain. New strategies may be needed to improve efficacy of SARS-CoV-2 variant vaccines.

Figure 1

Potential impact of repeated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-based vaccine boosting on antibody responses. Human antibodies against SARS-CoV-2 epitopes that are conserved across ancestral [wild type (WT)] and variants of concern (VOC) Spike proteins (blue) are elicited by initial WT vaccination and are likely to be boosted in response to subsequent VOC-targeted vaccines. The preferential recall of conserved immune responses imprinted to the WT strain may limit the generation of de novo responses against VOC receptor binding domain (RBD) epitopes (red and yellow) in response to booster vaccine doses. This figure was created using BioRender (https://biorender.com/).