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Cross-reactivity00:42

Cross-reactivity

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Overview
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Mapping SARS-CoV-2 antigenic relationships and serological responses.

Samuel H Wilks1, Barbara Mühlemann2,3, Xiaoying Shen4,5

  • 1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.

Biorxiv : the Preprint Server for Biology
|July 21, 2022
PubMed
Summary

SARS-CoV-2 variants challenge immunity, but antigenic cartography reveals how spike protein changes affect antibody responses. Vaccine effectiveness increases significantly over time, especially after the second dose.

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Area of Science:

  • Immunology
  • Virology
  • Vaccinology

Background:

  • Emergence of SARS-CoV-2 variants with immune escape properties raised concerns about vaccine and infection-induced protection.
  • Understanding the antigenic relationships between different SARS-CoV-2 variants and human immune sera is crucial for assessing current and future protection.

Approach:

  • Antigenic cartography was employed to map the antigenic relationships among 21 SARS-CoV-2 variants.
  • A panel of 15 human sera groups, collected after infection with 10 variants or vaccination (mRNA-1273, mRNA-1273.351), was used to analyze cross-reactivity patterns.

Key Points:

  • Antigenic divergence among pre-Omicron variants was attributed to specific substitutions in the spike protein (positions 417, 452, 484, 501).
  • Immune response breadth showed the most substantial increase between 4 weeks and over 3 months post-second vaccine dose.
  • Immunodominance of spike protein regions varied based on the initial variant exposure, impacting risk assessment and vaccine design.

Conclusions:

  • Antigenic cartography provides a quantitative framework for understanding SARS-CoV-2 variant evolution and immune responses.
  • The timing of immune response maturation and the impact of prior variant exposure are critical factors in determining protection against evolving viruses.
  • Findings inform strategies for variant risk assessment and the selection of optimal vaccine strains to address circulating SARS-CoV-2 variants.