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Differential immunity induced by Omicron sublineages in naïve and vaccine breakthrough infections

  • 0Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Scientific Reports +

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July 3, 2025

|

July 3, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Omicron sublineages like BQ.1.1 and XBB.1.5 show increased antibody evasion. Prior SARS-CoV-2 exposure may impair immune responses to these variants, contributing to their continued spread.

Area Of Science

  • Virology
  • Immunology
  • Infectious Diseases

Background

  • The Omicron variant of SARS-CoV-2 rapidly evolved into numerous sublineages.
  • These sublineages exhibited enhanced antibody evasion capabilities.
  • Understanding immune responses to these evolving variants is crucial for public health.

Purpose Of The Study

  • To quantify and compare neutralizing antibody titers against various SARS-CoV-2 variants.
  • To investigate the impact of prior infection or vaccination on immune responses to Omicron sublineages.
  • To assess the durability of cross-neutralizing antibody responses.

Main Methods

  • Live virus neutralization assays were performed.
  • Antibody titers were measured in 170 COVID-19 patients and 25 vaccinated controls.
  • Participants were infected with Delta or Omicron sublineages (BA.1, BA.2, BA.4/BA.5, BQ.1.1, XBB.1.5) or received a BA.5 bivalent booster.

Main Results

  • Vaccinated controls showed higher neutralizing titers against earlier Omicron sublineages (e.g., BA.5) than later ones (BQ.1.1, XBB.1.5).
  • In Omicron-infected patients, cross-neutralizing responses were weaker and less durable against later sublineages.
  • Self-neutralizing titers against BQ.1.1 or XBB.1.5 were lower than cross-neutralizing titers against earlier sublineages.

Conclusions

  • Prior SARS-CoV-2 exposure (infection or vaccination) may lead to "original antigenic sin," impairing responses to newer Omicron sublineages.
  • The reduced immunogenicity and increased antibody evasion of later Omicron sublineages contribute to their sustained global circulation.

Keywords:

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