Repeated Omicron infection dampens immune imprinting from previous vaccination and induces broad neutralizing antibodies against Omicron sub-variants

J Infect. 2024 Aug;89(2):106208. doi: 10.1016/j.jinf.2024.106208. Epub 2024 Jun 20.

Abstract

Objective: Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting has been found to limit the performance of updated vaccines based on the emerging variants of SARS-CoV-2. We aimed to investigate whether repeated exposure to Omicron variant could reduce the immune imprinting from previous vaccination.

Methods: A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed.

Results: Neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants, both in the vaccine naive and vaccine experienced individuals.

Conclusions: Our results demonstrate that repeated Omicron infection dampens immune imprinting from vaccination with WT SARS-CoV-2 and induces broad neutralizing profiles against Omicron sub-variants.

Keywords: Broad neutralizing; Immune imprinting; Omicron; Repeated infection; SARS-CoV-2.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Antigenic Drift and Shift / immunology
  • Broadly Neutralizing Antibodies / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunization, Secondary
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • Vaccination*

Substances

  • COVID-19 Vaccines
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies

Supplementary concepts

  • SARS-CoV-2 variants