Safety, Tolerability, and Immunogenicity of aH5N1 Vaccine in Adults with and Without Underlying Immunosuppressive Conditions.

: Pandemic influenza may cause substantial morbidity and mortality, especially in older adults and those with immunosuppressive conditions. : In this phase 3, stratified, randomized, controlled, observer-blind, multicenter trial, we evaluated the safety, tolerability, and immunogenicity of an adjuvanted H5N1 vaccine (aH5N1) vs. active control (MF59-adjuvanted trivalent seasonal inactivated influenza vaccine [aTIV]) in 539 adults aged 18-60 and ≥61 years. Participants were further stratified into subgroups that were healthy (18-60 years, n = 91; ≥61 years, n = 89) or had prespecified immunosuppressive conditions (18-60 years, n = 180; ≥61 years, n = 179). Antibody responses were measured with microneutralization and single radial hemolysis (SRH) assays. : aH5N1 increased antibody responses in healthy persons and those with immunosuppressive conditions in both age groups, with SRH geometric mean ratios (GMRs) > 2.5 and >2.0 in participants aged 18-60 and ≥61 years, respectively, meeting former Committee for Medicinal Products for Human Use (CHMP) criteria. Responses measured with the microneutralization and SRH assays were consistent with previous studies of aH5N1. : The aH5N1 vaccine had a clinically acceptable safety and tolerability profile with an AE profile comparable to that observed in previous aH5N1 studies. These findings support the viability of aH5N1 as a pre-pandemic influenza vaccine for the immunization of at-risk individuals when an antigenically matched pandemic influenza vaccine is not yet available.