Our results showed about what you would expect. Vaccines induce a strong antibody response against the part of SARS-CoV-2’s S protein found in the vaccine, but natural infection tends to produce antibodies against a greater number of unique S peptides. For example, if we rank study participants by the number of unique S peptides with an antibody response, the top 3 people had a natural infection.
The most significant difference is antibody production against the virus’s nucleocapsid protein (N). This protein is not a part of the vaccines, so vaccinated individuals did not generate N antibodies. However, each naturally infected person we tested showed significant N antibody production. Our observation is also reported elsewhere in the scientific literature.
Vaccines produce fewer unique antibodies, which are all directed against the viruses S protein. That gives the virus a greater chance to escape antibody protection than natural immunity. This is because the virus can escape vaccine immunity by only mutating its S protein. Whereas to escape natural immunity, the virus needs to mutate both the S and N protein. The broader antibody responses after natural infection explains natural immunity’s greater protection from a mechanistic perspective.
One of the important aspects of antibodies that target N, is that N has a much slower mutation rate than S. This further reduces the risk for reinfection in naturally immune individuals.
When variants arise, they usually escape from some, but not all antibodies produced after a vaccine. This is how breakthrough infections occur. Most people may not even notice the breakthrough infection. In those that do have a symptomatic breakthrough infection, the majority will experience less severe illness. This is because of the remaining partial immune protection.
People with natural immunity have more comprehensive immune protection. A reinfection should be even less severe than a breakthrough infection. Once most people have natural immunity it will be more difficult to transmit the virus. Emergence of variants should also slow.