Impact of the Spike Protein
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.
Evidence on S1 RBD
- 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.