SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants

PLoS Med. 2021 Jul 6;18(7):e1003656. doi: 10.1371/journal.pmed.1003656. eCollection 2021 Jul.


The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nucleocapsid Proteins / immunology
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Nucleocapsid Proteins

Grant support

This work was supported by Snow Medical (Australia, FB), The University of New South Wales Rapid Response grant (Australia, ADK), the University of Sydney Research Excellence Initiative grant (Australia, FB), the Medical Research Future Fund COVID-19 grant (MRFF2005760, SGT), Medical Research Future Fund Antiviral Development Call grant (DC), Medical Research Future Fund COVID-19 grant (MRFF2001684, ADK), the New South Wales Health COVID-19 Research Grants Round 2 (FB), and the Australian Governments for the provision of blood, blood products, and services for the Australian community (Australian Red Cross Lifeblood, IBG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.