Impaired neutralizing antibody efficacy of tixagevimab-cilgavimab 150+150 mg as pre-exposure prophylaxis against Omicron BA.5. A real-world experience in booster vaccinated immunocompromised patients

• Published in: Journal of clinical virology Vol. 168; p. 105584
• Main Authors: Schiaroli, Elisabetta, Gidari, Anna, Brachelente, Giovanni, Bicchieraro, Giulia, Spaccapelo, Roberta, Bastianelli, Sabrina, Pierucci, Sara, Busti, Chiara, Pallotto, Carlo, Malincarne, Lisa, Camilloni, Barbara, Falcinelli, Flavio, De Socio, Giuseppe Vittorio, Villa, Alfredo, Mencacci, Antonella, Francisci, Daniela
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2023
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; Cilgavimab; Humans; Immunocompromised Host; Immunocompromised subjects; Immunoglobulin G; Neutralization activity; Pre-Exposure Prophylaxis; SARS-CoV-2; Tixagevimab; VOCs; RCT; Tixagevimab; NT-Abs; RBD; Cilgavimab; Neutralization activity; Immunocompromised subjects; Pre-exposure prophylaxis; HCW; Sars-CoV-2
• ISSN: 1386-6532; 1873-5967; 1873-5967
• DOI: 10.1016/j.jcv.2023.105584

•Evusheld should be considered an integration, not a substitute, of vaccination against SARS-CoV-2.•To date, pre-exposure prophylaxis with tixagevimab-cilgavimab (300 + 300 mg) is mandatory.•The threshold defining protection on antibody neutralisation efficacy was an NT-Abs titre of 8. Tixagevimab-cilgavimab has been approved as primary pre-exposure prophylaxis in immunocompromised patients as support or replacement for vaccination, even though the Omicron variant of concern (VOC) was spreading at the time. The aim of our study was to evaluate the post-injection neutralising activity (NT90-Abs titre) against the Omicron BA.5 variant in fully vaccinated immunocompromised patients. NT90-Abs titres against BA.5 and 20A.EU1 as well as anti-spike and anti-receptor-binding domain IgG were evaluated 0, 14, and 30 d after tixagevimab-cilgavimab administration. The primary end point was NT90-Abs titres ≥ 80 against BA.5 in ≥ 25% of patients, and the secondary end point was NT90-Abs titres ≥ 1280 against 20A.EU1 in >50% of patients on day 14. At baseline, 35.2%, 37.02%, and 32.5% of booster vaccinated patients exhibited undetectable levels of anti-S and anti-RBD IgG antibodies such as NT90-Abs titres against A20.EU1. Moreover, 35 patients (61.5%) had undetectable NT90-Abs titres against BA.5. On day 14, IgG anti-S and anti-RBD levels were 3880 BAU/mL and 776.6 AU/mL, respectively. Only 12.5% of patients met a NT90-Abs titres ≥ 80 against BA.5, whereas the median NT90-Abs titre against 20A.EU1 was 1280. NT90-Abs titres against BA.5 were 64-fold lower than those against A20.EU1. Four patients (7.5%) had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the 3 months after treatment, all with a time gap between the booster vaccination and injection. To date, tixagevimab-cilgavimab cannot be considered a substitute for vaccination but may be a useful supporting therapy if the recommended dose for pre-exposure prophylaxis is doubled.