Despite effective spike-based vaccines and monoclonal antibodies, the SARS-CoV-2 pandemic continues more than two and a half years post-onset. Relentless investigation has outlined a causative dynamic between host-derived antibodies and reciprocal viral subversion. Integration of this paradigm into the architecture of next generation antiviral strategies, predicated on a foundational understanding of the virology and immunology of SARS-CoV-2, will be critical for success. This review aims to serve as a primer on the immunity endowed by antibodies targeting SARS-CoV-2 spike protein through a structural perspective. We begin by introducing the structure and function of spike, polyclonal immunity to SARS-CoV-2 spike, and the emergence of major SARS-CoV-2 variants that evade immunity. The remainder of the article comprises an in-depth dissection of all major epitopes on SARS-CoV-2 spike in molecular detail, with emphasis on the origins, neutralizing potency, mechanisms of action, cross-reactivity, and variant resistance of representative monoclonal antibodies to each epitope.

Original languageEnglish
Title of host publicationAdvances in Immunology
EditorsFrederick W. Alt, Kenneth M. Murphy
PublisherAcademic Press Inc.
Number of pages69
ISBN (Print)9780323989435
StatePublished - Jan 2022

Publication series

NameAdvances in Immunology
ISSN (Print)0065-2776
ISSN (Electronic)1557-8445


  • Coronavirus cross-reactivity
  • N-terminal domain antibody
  • Neutralizing variants of concern
  • Receptor-binding domain antibody
  • S2 antibody
  • SARS-CoV-2 neutralizing antibody
  • SARS-CoV-2 spike antibody
  • Spike epitopes


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