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

Background: 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.

Objectives: 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.

Study design: 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.

Results: 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.

Conclusions: 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.