Pandemic Influenza Vaccine in Organ Transplantation (PIVOT Trial)

Influenza is an important pathogen in transplant recipients. The current widespread outbreak of highly pathogenic H5N1 avian influenza (HPAI) in livestock, and the occurrence of several human cases of infection suggest that the next influenza pandemic may be soon approaching. Transplant patients will likely be uniquely predisposed to serious infection with high morbidity and mortality. There are a number of important reasons that evaluation of prevention strategies are critical in this highly vulnerable population. Currently, there is no data on the immunogenicity of H5Nx vaccines in this highly vulnerable population. The investigators plan to study the safety and immunogenicity of a two-dose regimen of the pandemic influenza H5N1 vaccine in organ transplant patients.

This randomized, placebo-controlled, double-blind, single-centre trial will evaluate the immunogenicity and safety of a two-dose regimen of the AS03-adjuvanted inactivated H5N1 vaccine (AREPANRIX™ H5N1, GSK) in adult organ transplant recipients. A total of 120 stable outpatient organ transplant recipients at the University Health Network (Toronto, Canada) will be enrolled and randomized 1:1 to receive two doses of H5N1 vaccine or placebo (0.9% saline) administered intramuscularly 3 weeks apart. Blood samples collected at baseline (V0), 3 weeks (V1), and 6 weeks (V2) will be analyzed for serologic responses using hemagglutination inhibition (HAI) assays against vaccine and circulating H5N1 strains. In a subset of 60 participants (30 per arm), peripheral blood mononuclear cells will be obtained at each time point to assess cell-mediated immunity, including H5-specific CD4+ and CD8+ T-cell cytokine responses and B-cell immunity. Participants will be monitored for local and systemic adverse events for 7 days following each dose and followed for 6 months for any adverse events, including rejection, influenza-like illness, and laboratory-confirmed influenza. Long-term immunogenicity will also be assessed at 6 months in vaccine recipients.