Neutralizing Antibody Response to Sarbecovirus Is Delayed in Sequential Heterologous Immunization

Viruses. 2022 Jun 24;14(7):1382. doi: 10.3390/v14071382.

Abstract

Antigenic imprinting, which describes the bias of the antibody response due to previous immune history, can influence vaccine effectiveness. While this phenomenon has been reported for viruses such as influenza, there is little understanding of how prior immune history affects the antibody response to SARS-CoV-2. This study provides evidence for antigenic imprinting through immunization with two Sarbecoviruses, the subgenus that includes SARS-CoV-2. Mice were immunized subsequently with two antigenically distinct Sarbecovirus strains, namely SARS-CoV-1 and SARS-CoV-2. We found that sequential heterologous immunization induced cross-reactive binding antibodies for both viruses and delayed the emergence of neutralizing antibody responses against the booster strain. Our results provide fundamental knowledge about the immune response to Sarbecovirus and important insights into the development of pan-sarbecovirus vaccines and guiding therapeutic interventions.

Keywords: COVID-19; SARS-CoV-2; antigenic imprinting; coronavirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing*
  • Antibodies, Viral
  • Antibody Formation
  • COVID-19* / prevention & control
  • Immunization
  • Mice
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This work was supported by Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Disease (20191205) (C.K.P.M.), Emergency Key Program of Guangzhou Laboratory (Grant No. EKPG22-30-6) (C.K.P.M, M.P.), Calmette and Yersin scholarship from the Pasteur International Network Association (H.L.), start-up fund from the University of Illinois at Urbana-Champaign (N.C.W.), visiting scientist scheme from Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore (C.K.P.M.), and the Bill & Melinda Gates Foundation (INV-004923) (N.C.W.).