People who had COVID-19 before or after vaccination have the most robust and most stable immunity to coronavirus. The immunity of such people is called hybrid. Hybrid immunity occurs because different neutralizing antibodies respond to natural infection and vaccination.
Only antibodies to the coronavirus spike protein (S-antibodies) have neutralizing activity. However, after infusion with the cell, the spike protein changes shape, affecting the antibody’s neutralizing activity.
The figure below shows the closed and open conformations of the S protein. These conformations differ in the position of the three RBD fragments of the spike protein: standing or lying. Before binding to ACE2 and entering cells, the S-protein remains in a closed-conformation – RBD fragments are supine. The open conformation of the spike protein is characterized by the standing position of the RBD, which allows the coronavirus to bind to the ACE2 receptor and enter the cell. Therefore, depending on whether the SARS-CoV-2 spike protein entered the body through ACE2 or with the help of a vaccine, antibodies to the S-protein will differ.
Image source: https://www.mdpi.com/1422-0067/23/4/2078/htm
Four Classes of Neutralizing Antibodies
Belgian scientists investigated neutralizing antibodies and divided them into four classes according to their ability to bind open and closed conformations of the coronavirus spike protein. Each class of neutralizing antibodies targets specific conformations of spike proteins:
- NTD are neutralizing antibodies that can bind to the NTD nucleocapsid protein if the shape of the spike protein is closed, 1-open, and 3-open.
- RBD-Closed – neutralizing antibodies that bind to the spike protein in closed and open conformation.
- RBD-Open-LowClash – neutralizing antibodies that cannot bind to the closed conformation of the spike protein but bind to the open conformation.
- RBD-Open-HighClash are neutralizing antibodies that cannot bind to either the closed or 1-open conformation of the spike protein. They can only link to 2-open or 3-open conformations.
Fragments of the spike protein that are important for attachment to the ACE2 receptor can be bound by neutralizing antibodies of the RBD-Closed and RBD-Open-LowClash classes.
The spike protein fragments that neutralize the RBD-Closed class’s antibodies can often bind to mutate in circulating coronavirus strains. Therefore, the neutralizing ability of this class of antibodies depends on the SARS-CoV-2 strain. The neutralizing ability of RBD-Open-LowClash antibodies is less affected by mutations.
Neutralizing Classes of Post-Vaccine and Natural COVID-19 Antibodies
Scientists investigated which classes of neutralizing antibodies to RBD are present in people who have recovered from COVID-19 and in people who have not been vaccinated with the disease:
- After COVID-19, antibodies of the RBD-Closed class are produced, binding to the spike protein’s closed and open conformations.
- After vaccination, antibodies of the RBD-Open-LowClash class are predominantly produced. These antibodies cannot bind to the closed conformation of the SARS-CoV-2 spike protein.
The ability to neutralize antibodies to bind to the closed conformation of the spike protein is probably more important than the ability to bind to fragments that attach to ACE2. Antibodies to the closed conformation of the S-protein block its transition to the open state and resist fusion with the cell.
Conclusions
Only one neutralizing antibody class can bind to the spike protein in closed and open conformations. This class is dominant in people who have had COVID-19. Vaccinated people are dominated by another class of antibodies that can only bind to the spike protein in an open conformation.
Natural infection and vaccines cause the production of neutralizing antibodies of different classes. Therefore, a hybrid immunization with a vaccine and a natural disease elicits a more substantial and more sustained immune response.
Neutralizing antibodies that recognize the S-protein in the closed state play a vital role in forming the immune response and are essential for protection against infection. Therefore, the S-protein in the closed state can become the basis of a new generation of coronavirus vaccines.
Useful article, necessary information? Share it!
Someone will also find it useful and necessary:
