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Related Experiment Video

Updated: Sep 16, 2025

Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research
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Exposure to two antigenically distinct SARS-CoV-2 variants broadens neutralization patterns.

Melanie M Schmitt1, Annika Rössler2, Antonia Netzl3

  • 1Institute of Virology, Department of Hygiene, Microbiology and Virology, Medical University of Innsbruck, Peter-Mayr-Str. 4b, 6020 Innsbruck, Austria.

Vaccine
|July 5, 2025
PubMed
Summary
This summary is machine-generated.

Sequential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures boost existing immunity and broaden antibody responses. However, subsequent variant exposures primarily enhance cross-reactivity rather than inducing new variant-specific antibodies.

Keywords:
Cross-neutralizationImmune imprintingNeutralizing antibodiesSARS-CoV-2

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Area of Science:

  • Immunology
  • Virology
  • Infectious Diseases

Background:

  • Previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants shapes subsequent neutralizing antibody responses.
  • Consecutive exposures tend to reinforce pre-existing immunity and expand cross-neutralizing antibodies, with limited induction of de novo variant-specific responses.

Purpose of the Study:

  • To analyze neutralizing antibody responses against various SARS-CoV-2 variants after exactly two exposures.
  • To investigate the impact of antigenically distinct variant exposures on neutralization breadth and specificity.
  • To explore the phenomenon of immune imprinting in SARS-CoV-2 infection and vaccination.

Main Methods:

  • Analysis of neutralizing antibodies in plasma samples from individuals with defined double exposure histories (pre-Omicron/pre-Omicron, pre-Omicron/Omicron, Omicron/Omicron).
  • Assessment of antibody neutralization against a panel of SARS-CoV-2 variants.
  • Depletion experiments to determine the influence of initial variant exposure on antibody specificity.

Main Results:

  • Exposure to two antigenically distinct variants (e.g., pre-Omicron followed by Omicron) increased antibody neutralization breadth.
  • No significant cross-neutralization was induced against the closely related human coronavirus SARS-CoV.
  • Antibody specificity was strongly influenced by the first variant exposure, with the second exposure primarily expanding cross-reactive antibodies, not inducing new variant-specific responses.

Conclusions:

  • Multiple SARS-CoV-2 exposures enhance cross-neutralization against diverse variants, demonstrating broadened immunity.
  • The phenomenon of immune imprinting is evident, where initial exposures dictate the antibody response profile to subsequent variant encounters.
  • There is a limited capacity for de novo antibody production against more recently encountered SARS-CoV-2 variants following prior exposures.