Impact of COVID-19 Monoclonal Antibody Therapy on Subsequent Vaccine-elicited SARS-CoV-2 Immune Responses

Background How anti-SARS-CoV-2 monoclonal antibodies (mAbs) change subsequent vaccine responses remains uncertain. Methods We conducted a prospective, phase IV, open-label study of adults who received mRNA-1273 or BNT162b2. Cohort 1 included outpatients with acute COVID-19 previously randomized to mAbs (tixagevimab/cilgavimab or amubarvimab/romlusevimab), camostat, or placebo in ACTIV-2/A5401. Cohort 2 included unvaccinated adults without reported prior COVID-19 and was analyzed as naïve or non-naïve by baseline neutralizing antibodies (nAbs). We measured binding IgG, nAbs, spike-specific memory B cells, and CD4+/CD8+ T cells at baseline and days 28, 56, and 140. Results Forty-three participants were analyzed. At day 140, nAb titers were lower among prior mAb recipients and COVID-19–naïve participants than among placebo/camostat recipients and those with evidence of prior infection (overall p=0.018). RBD-specific, but not spike-specific, memory B cells were reduced after prior mAb therapy at days 56 and 140. Frequency of spike-specific CD4+ and CD8+ T-cell responses did not differ by prior mAb exposure. Adverse events were mostly grade 1–2 and consistent with vaccine trials. Conclusions Prior anti-SARS-CoV-2 mAb treatment limits endogenous RBD-focused B-cell responses to later mRNA vaccination without measurably affecting T-cell immunity. Timing of vaccination after mAb therapy may matter and warrants study. Trial registration NCT04952402.