Immunogenicity and safety of tixagevimab-cilgavimab for COVID-19 pre-exposure prophylaxis in immunocompromised 20 to <40 kg children and adolescents: A pilot, prospective, open-labeled study

Abstract

We evaluated the immunogenicity of 300 mg Tixagevimab-Cilgavimab in immunocompromised children and adolescents who weighed 20 to >40 kg. Six to 18-year-old participants were divided into two groups by body weight and received 300 mg (20 to <40 kg) and 600 mg (≥40 kg) Tixagevimab-Cilgavimab, respectively. Anti-SARS-CoV-2 receptor-binding domain IgG concentrations and pseudovirus neutralizing antibody (NAb) titers were measured at 4, 12, and 24 weeks after administration and compared with reference data from healthy Thai children at 2 weeks after three BNT162b2 vaccinations. Of 59 participants, 49.2% were female, with a median (IQR) age of 12 (9, 15) years; 16 (27.1%) had cancer. NAb titers (95% CI) for the ancestral Wuhan strain were comparatively high for both dosing regimens (16363.2 [13765.9, 19450.5] vs 17768.3 [15539.5, 20316.9] in 20 to <40 kg and ≥40 kg participants, respectively) and significantly higher than reference titers (P < 0.001 for both). NAb titers for Omicron BA.4/5 were on par with the reference for both dosing regimens. Adverse events were mild, well tolerated, and slightly more prevalent in ≥40 kg participants who received full-dose Tixagevimab-Cilgavimab. Minimal waning in anti-RBD IgG concentrations, comparable to the reference, was observed at 12 and 24 weeks after Tixagevimab-Cilgavimab administration for both regimens. We concluded that half-dose Tixagevimab-Cilgavimab in 20 to <40 kg participants generated equivalent antibodies to standard doses in ≥40 kg participants and significantly higher antibodies than three-dose BNT162b2 vaccination. Further study of monoclonal long-acting antibodies in larger cohorts and <6-year-old children are warranted.

Keywords: COVID-19; Thailand; Tixagevimab-cilgavimab; adolescents; children; immunocompromised; long-acting antibody; monoclonal antibody; pre-exposure prophylaxis.

Figure 1.

Consort flow diagram. Sixty participants were screened and 59 enrolled and allocated into their respective weight groups. Fifty participants were included at baseline after excluding those who were COVID-19 positive (tested IgM or anti-NP positive). Blood samples were assessed at 4, 12, and 24 weeks after antibody administration. Participants who tested positive for COVID-19 or were lost to follow-up were excluded from analyses of subsequent visits.

Figure 2.

Anti-SARS-CoV-2 receptor binding domain (RBD) IgG geometric mean concentrations (GMCs) at 4, 12, and 24 weeks after Tixagevimab-Cilgavimab administration. Anti-RBD IgG GMCs of healthy children after three doses of BNT162b2 were included as a reference. Abbreviations: BAU, binding antibody units.

Figure 3.

Geometric mean titers (GMTs) of neutralizing antibodies (NAb) from 50% pseudovirus neutralization tests (PVNT₅₀) against (a) the ancestral (Wuhan) strain and (b) Omicron BA.4/5 subvariant. PVNT₅₀ NAb GMTs of healthy children after three doses of BNT162b2 were included as a reference. Titer values below the lower limit of detection (LLOD of 1:40) were replaced with 20. Error bars represent geometric means with 95% confidence intervals.

Figure 4.

Self-reported mild and moderate systemic and local adverse events within seven days of Tixagevimab-Cilgavimab administration by weight group.