Pandemic Influenza Vaccine in Organ Transplantation (PIVOT Trial)

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.

Inclusion criteria

• Age ≥ 18 and greater than 3 months post-transplant
• Stable graft function
• eGFR >30mL/min/1.73m2
• Able to provide informed consent

Exclusion criteria

• Allergy to vaccine components;
• Previous life-threatening reaction to influenza vaccine (ie Guillain Barré Syndrome);
• Ongoing or recent therapy for acute rejection (within the previous 30 days);
• Ongoing active cytomegalovirus (CMV) infection with viral load of greater or equal to 1000 international units/ml in the last 7 days;
• Febrile illness in the past 2 weeks;
• Rituximab in the last 6 months;
• Receiving treatment for active or acute infection;
• Unable to provide informed consent;
• 2025 seasonal influenza vaccination in preceding 6 weeks;
• Recent other vaccination in last 14 days;
• Receipt of intravenous immunoglobulin in last 30 days or expected to receive in next 30 days; Life expectancy < 3 months;
• Diagnosis of influenza virus infection in the last 90 days.
• Pregnancy known at the time of enrolment