Early Flu Shots in SOT

Study Overview
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Brief Summary
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Although time from transplant has been a factor in vaccine response, there is limited data on immunizations that occur in the first post-transplant year, and there are no data that suggest influenza vaccination early post-transplant may have any adverse effects on the graft. It is suggested that early vaccinations may lead to reduced immunogenicity due to induction immunosuppression. However, not vaccinating patients may leave them vulnerable to influenza infection for a period of time. This study is designed to look at the immunogenicity and side effects of the standard of care influenza vaccine in patients between 31 and 365 days post-transplant.

Detailed Description
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Influenza virus is an important cause of morbidity in the transplant population and can lead to viral and bacterial pneumonia. Influenza vaccine is effective in the prevention of influenza infection and is recommended by the Canadian National Advisory Committee on Immunization (NACI). The annual influenza vaccine is suggested for transplant patients as the standard of care starting from 3 months post-transplant. Most recent guidelines now suggest that it is reasonable to get a flu shot starting earlier at 1 month post-transplant. Anti-rejection drugs are now tapered more quickly and it is possible that antibodies will be produced against the flu shot as early as 1 month post-transplant. The study hypothesizes that kidney and liver transplant recipients in the early post-transplant period (31-180 days) will have similar immunogenicity as those in the late post-transplant period (>180 days).

Official Title
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Safety and Immunogenicity of Influenza Vaccine During the First Post-Transplant Year in Solid Organ Transplant Recipients

Conditions
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Influenza, Solid Organ Transplant

Intervention / Treatment
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* Biological: standard of care influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney, liver or pancreas transplant recipients on at least one immunosuppressive medication Age ≥ 18 Outpatient status Greater than 30 days post-transplant Exclusion Criteria: Has already received influenza vaccination for 2017-2018 season Egg allergy or allergy to previous influenza vaccine Febrile illness in the past one week Active Cytomegalovirus viremia Use of Rituximab in the past one year Ongoing or recent (in past 30 days) therapy for acute rejection Chronic kidney insufficiency (creatinine clearance ≤30mL/min or dialysis-dependent Previous life-threatening reaction to influenza vaccine (i.e., Guillain Barre Syndrome) Receipt of intravenous immunoglobulin (IVIG) in the past 30 days or planning to receive IVIG in the next four weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 31-90 days<br>Patient 31-90 days after transplantation receiving standard of care annual 2017-2018 influenza vaccine. | Biological: standard of care influenza vaccine<br>* The standard of care annual 2017-2018 influenza vaccine will be used for this study.<br>* Other names: annual influenza vaccine;|
| 91-180 days<br>91-180 days after transplantation receiving standard of care annual 2017-2018 influenza vaccine. | Biological: standard of care influenza vaccine<br>* The standard of care annual 2017-2018 influenza vaccine will be used for this study.<br>* Other names: annual influenza vaccine;|
| 181-365 days<br>181-365 days after transplantation receiving standard of care annual 2017-2018 influenza vaccine. | Biological: standard of care influenza vaccine<br>* The standard of care annual 2017-2018 influenza vaccine will be used for this study.<br>* Other names: annual influenza vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine immunogenicity | Vaccine immunogenicity based on assessment of pre- and post-vaccine (4 weeks) antibody titer. A positive vaccine response will be defined based on: Seroconversion rate: serological response with a four-fold or greater increase in HAI antibody titers to each of the three antigens in the vaccine, and Seroprotection rate: HAI titers of ≥1:40 to each of the three antigens post-immunization. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety- adverse events | Local and systemic adverse events to vaccination | 7 days | 
| Safety- graft rejection | Rates of biopsy proven allograft rejection in the 6 months following vaccination | 6 months | 
| Safety- HLA | Development of de novo or increased titer of HLA alloantibody and specifically DSA (donor specific antibody). The 4 weeks post-vaccine sample will be compared with the pre-vaccine samples. | 4 weeks | 
| Vaccine efficacy- CMI | Analysis of CMI in a subgroup of 60 patients (influenza strain-specific CD4+ and CD8+ T-cell responses; detectable vs. non-detectable and absolute percentage) at four weeks post-vaccine vs. pre-vaccine sample. CMI responses will also be correlated with HAI responses. | 4 weeks | 
| Vaccine efficacy- infection | Documented influenza infection (i.e., microbiology proven by the direct fluorescent antibody, viral culture, or PCR) in the six months following vaccination. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine immunogenicity, vaccine safety