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 naive or non-naive 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-naive participants than among placebo/camostat recipients and those with evidence of prior infection (overall P = .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. CLINICAL TRIALS REGISTRATION: NCT04952402.