RESULTS
The neutralizing activity of mRNA-1273 vaccine–elicited antibodies is more RBD-targeted than that of infection-elicited antibodies
We studied sera from adults (ages 18 to 55 years) who received two doses of the Moderna mRNA-1273 vaccine in phase 1 clinical trials (12). The majority of our study focused on
14 individuals who received the 250-μg dose, although we validated key conclusions with
a smaller subset of eight trial participants who received the 100-μg dose. The sera were collected at 36 and 119 days after the first vaccine dose, corresponding to 7 and 90 days after the second dose. It was previously shown that these individuals had high amounts of binding and neutralizing antibodies against SARS-CoV-2, with neutralizing antibody titers within the upper quartile of sera from SARS-CoV-2 convalescent individuals (12). Throughout, we compared vaccine sera to convalescent plasma or serum samples from two independent cohorts (13, 14). The convalescent plasma samples were characterized in earlier studies (13–16) and grouped into an early time point of 15 to 60 days after symptom onset and a late time point of 100 to 150 days after symptom onset.
The majority of the neutralizing activity of convalescent sera and plasma is due to RBD-binding antibodies (15, 17, 18). To determine whether neutralization by vaccine sera is similarly RBD-targeted, we depleted RBD-binding antibodies from the day 36 and 119 sera isolated from
14 individuals who received the 250-μg dose of the mRNA-1273 vaccine. We then measured serum immunoglobulin G (IgG) binding to the RBD and full spike ectodomain before and after depletion. As expected, depletion removed all RBD-binding antibodies (Fig. 1A and fig. S1, A and B). However, depleting RBD-binding antibodies only moderately decreased spike-binding activity in either vaccine sera or convalescent plasma (Fig. 1B and fig. S1B), consistent with studies showing that a minority of spike-binding vaccine-elicited B cells target the RBD (5, 19)....
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