SARS-CoV-2 Spike Protein AntibodiesScientific evidence can help strengthen our understanding of COVID-19 immune response

Neutralizing antibodies are one of our immune system’s most important tools for fighting viral infections, including COVID-19.

The spike protein is a structure of the SARS-COV-2 virus that includes the S1 receptor-binding domain (RBD). The S1 RBD is instrumental for allowing the SARS-CoV-2 virus to reproduce by attaching to and infecting host cells.¹

Antibodies that target and bind to the S1 RBD have shown strong correlation to neutralization, while evidence for neutralizing antibodies to the Nucleocapsid (N) protein is sparse.^2,3

In fact, available vaccines have been designed specifically to spur the immune system into creating antibodies to the S1 RBD antigen.4 Given this, understanding the evidence for different antibodies to neutralize SARS-CoV-2 will likely prove valuable for assessing immune response to the virus and its vaccines.

• As the SARS-CoV-2 spike protein antibody decays slower over time, assays to the spike protein are a more reliable target for serological assays in the longer term. There was a significant correlation between spike/RBD antibody and ACE-2 receptor blocking activity.
  Grandjean, L. Humoral response dynamics following infection with SARS-CoV-2. medRxiv. 2020. doi: https://doi.org/10.1101/2020.07.16.20155663.
• Neutralizing antibodies directed against the spike protein appear most appropriate for prognostication of protection/immunity, compared to N antibodies.
  Muecksch, F. Longitudinal analysis of clinical serology assay performance and neutralizing antibody levels in COVID19 convalescents. medRxiv. 2020. doi: https://doi.org/10.1101/2020.08.05.20169128.
• “Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.”
  McAndrews, K. Heterogeneous antibodies against SARS-CoV-2 spike protein receptor binding domain and nucleocapsid with implications for COVID-19 immunity. 2020. JCI Insight. doi: https://doi.org/10.1172/jci.insight.142386.