Serum Virus-Neutralizing Antibody Titers in Clinical Trial Participants With and Without Immunocompromise Receiving Pemivibart, a Long-Acting Monoclonal Antibody for COVID-19

Background: Pemivibart received emergency use authorization for COVID-19 prevention in certain individuals with immunocompromise based on immunobridging calculated serum virus-neutralizing antibody (csVNA) titers. We report an analysis of measured (msVNA) titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants before and after receipt of pemivibart in a SARS-CoV-2 immune-experienced population (CANOPY) and compare the relationship between csVNA and msVNA titers in 2 clinical trials. Methods: The trials were conducted during 2023–2024. In the phase 3 CANOPY trial, participants with (cohort A) or without (cohort B) significant immunocompromise received 2 intravenous 4500-mg pemivibart or placebo infusions 90 days apart. In the phase 1 trial, healthy adults received a single intravenous dose of pemivibart (1500, 2500, or 4500 mg). msVNA titers were determined using a SARS-CoV-2 spike pseudotyped assay; csVNA titers were calculated as serum pemivibart concentrations divided by variant-specific IC50 values from in vitro neutralization assays. Results: In CANOPY, predose msVNA geometric mean titers (GMTs) to the dominant circulating XBB.1.5 lineage were low across cohorts (range, 78.6–119.8), suggesting inadequate protection. msVNA titers were substantially higher against earlier Delta (B.1.617.2) and BA.4/5 variants. Pemivibart increased the day-28 msVNA GMT >55-fold against XBB.1.5, with similar levels in both cohorts. Across trials, csVNA titers were significantly correlated with msVNA titers (all Spearman correlation coefficients ≥0.73, P < .0001). Conclusions: These data show that previous immune experience to earlier pandemic variants provided limited cross-protection and demonstrate that pemivibart increased protective titers against newly circulating SARS-CoV-2 in individuals with and without immunocompromise. Notably, csVNA titers effectively predicted pemivibart's neutralization potential. Clinical Trials Registration. NCT06039449 and NCT05791318. © The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.