Deep immunological imprinting due to the ancestral spike in the current bivalent COVID-19 vaccine

• DOI: 10.1016/j.xcrm.2023.101258
• Publication Date: 2023-10-30T15:13:11Z
• Authors: Qian Wang; Yicheng Guo; Anthony R. Tam; Riccardo Valdez; Aubree Gordon; Lihong Liu; David D. Ho
• Keywords: Bivalent (engine); Imprinting (psychology)

To combat the evolving SARS-CoV-2 Omicron variants, bivalent COVID-19 mRNA vaccines, encoding both ancestral and BA.5 spikes, have replaced monovalent vaccines in numerous countries. However, fourth doses of either vaccine result similar neutralizing antibody titers against subvariants, raising possibility immunological imprinting. address this, we investigate responses 72 participants given three a vaccine, followed by or booster, those with breakthrough infections BQ. Bivalent boosters do not show notably higher binding virus-neutralizing various variants compared to ones. lead significantly better neutralization subvariants. Multiple analyses, including antigenic mapping, suggest that spike is causing deep imprinting, preventing broadening antibodies component, thereby defeating its intended goal. Its removal from future compositions therefore strongly recommended.