Effect of Tezepelumab on the Humoral Immune Response to Seasonal Quadrivalent Influenza Vaccination in Patients with Moderate to Severe Asthma: The Phase3b VECTOR Study.

Abstract

Annual influenza vaccinations are recommended for adolescents and adults with moderate to severe asthma. This study investigated the effect of tezepelumab, a human monoclonal antibody that blocks theactivity of thymic stromal lymphopoietin, on the humoral immune response to the quadrivalent seasonal influenza vaccine in patients with moderate to severe asthma. VECTOR was a phase3b, randomized, multicenter, double-blind, parallel-group, placebo-controlled study. Adolescents (aged12-17years) and young adults (aged18-21years) with moderate to severe asthma were enrolled across 15 centers in the USA. Patients received tezepelumab 210mg or placebo subcutaneously at weeks0, 4, 8, and 12, and a single dose of inactivated quadrivalent seasonal influenza vaccine at week12 before receiving study treatment. Immediately before vaccination and at 4weeks postvaccination (week16), strain-specific antibody responses were assessed for four influenza antigens by hemagglutination inhibition (HAI) and microneutralization (MN) assays. Safety was assessed. Seventy patients were randomized to tezepelumab (n = 35) or placebo (n = 35). There were no meaningful differences in HAI or MN antibody responses between treatment groups at week16. HAI assay geometric mean fold rises (GMFRs) for influenza strains were 1.76-7.34 for tezepelumab and 1.46-4.75 for placebo. MN assay GMFRs were 4.00-14.56 for tezepelumab and 3.56-10.62 for placebo. In the HAI assay, a fourfold or larger rise in antibody titer from weeks 12 to 16 occurred in 15.2-78.8% and 15.2-51.5% of tezepelumab and placebo recipients, respectively, and 97.0-100% of patients in both treatment groups achieved an antibody titer of at least40 at week16. No unexpected safety findings occurred. There was no observed suppression of the humoral immune response after influenza vaccination in adolescents and young adults with moderate to severe asthma treated with tezepelumab. Therefore, the influenza vaccine can be administered to this patient population during tezepelumab treatment. NCT05062759.