Article
作者: Heaps, Amy L ; Li, Jonathan Z ; Bender Ignacio, Rachel A ; Ramirez, Sydney ; Javan, Arzhang Cyrus ; Coelho, Camila H ; Wohl, David Alain ; Parikh, Urvi M ; Myers, Amber ; Daar, Eric S ; Benson, Constance A ; Greninger, Alexander L ; Dhillon, Preeti K ; Crotty, Shane ; Aziz, Mariam ; Sieg, Scott F ; Hyer, Randall ; Manne-Goehler, Jennifer ; Lopez, Paul G ; Weir, Isabelle R ; Ramezani-Rad, Parham ; Wu, Xingye ; Chew, Kara W ; Faraji, Farhoud ; Smith, Davey M ; Bloom, Nathaniel
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.