Antibodies Produced Post-vaccination Different from Natural Infection

Researchers tested the antibodies elicited from mRNA vaccination and compared them to those from natural SARS-CoV-2 infection. They found the vaccine did not have antibodies to the virus nucleocapsid protein but had potent RBD antibodies. Researchers from the University of California investigated the immune response produced by the mRNA vaccines. Samples from vaccinated individuals were collected in January, February, and March 2021. They used the coronavirus antigen microarray to measure antibodies against 37 coronaviruses and influenza antigens. Since the vaccine does not have the nucleocapsid protein, there are no antibodies against this in the vaccine-induced antibodies.

However, antibodies against nucleocapsid were seen in natural infection, suggesting this could be a biomarker for natural infection. Vaccinated individuals showed high antibody levels against the full-length spike protein, S2 subunit, and much higher levels to the RBD and S1 subunit. These individuals also had cross-reactive antibodies between the spike protein and RBD, absent in natural infection. The mRNA vaccine likely adopts a protein conformation that presents cross-reactive epitopes. This could be useful against emerging virus variants and suggests the antibodies produced could still be effective against them. Antibodies from natural infection do not have high levels against the RBD.

This could be because the RBD epitope may be hidden to prevent host immune recognition. The less robust and variable antibody response to natural infection suggests immunity acquired by natural infection may not be as strong as that from vaccination. “We should not assume that previously infected individuals are immune or that they cannot transmit the virus,” write the authors. Thus, vaccination induces a more robust antibody response, and even people who have been previously infected may benefit from the vaccine.

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