Pre-exposure prophylaxis with Evusheld™ elicits limited neutralizing activity against the omicron variant in kidney transplant patients

The combination of cilgavimab-tixagevimab (Evusheld™, Astra Zeneca) became the mainstay for protecting transplant recipients with poor response to vaccination against the omicron variant. Serum neutralizing capacity against SARS-CoV-2 is positively associated with protection against severe forms of Covid-19.

Both anti-RBD IgG titers and neutralizing antibody titers against the omicron BA.1 variant were measured in serum samples collected from 63 adult kidney transplant recipients who received prophylactic injections of Evusheld™. Patients who received prophylactic Ronapreve™ (casirivimab-imdevimab, n = 39) and those who were infected with SARS-CoV-2 during the fifth wave of the pandemic (n = 14) served as negative and positive controls, respectively.

After a median interval from injection of 29 days (interquartile range 29-33 days), only 9.5% of patients who received Evusheld™ were able to neutralize the omicron variant compared to 71% of patients who were infected with SARS-CoV-2 and 2.6% of those who received Ronapreve™. Interestingly, convalescent patients displayed higher levels of neutralizing antibodies than those who received EvusheldTM (median: 2.3 log IC50, IQR: 1.5-2.7 versus 0.00 log IC50, IQR: 0&[ndash] 0.05; p<0.001). A high interindividual variability in anti-RBD IgG titers was observed after Evusheld™ (range: 262-7032 BAU/mL). This variability was largely explained by the patients’body mass index, which showed an inverse correlation with anti-RBD IgG titers.

These findings suggest that Evusheld™ given at a dose of 300 mg is not sufficient to elicit an anti-RDB titer that confers in vivo neutralizing activity and support recent FDA recommendations, derived from in vitro models, regarding the need to increase the dose of Evusheld™