Study of the Impact of Time of Vaccination on Response to Influenza Vaccine in Kidney Transplant Recipients -ChronoVAX

Study Overview
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Brief Summary
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Immune response to influenza vaccine in kidney transplant patients

Detailed Description
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Seasonal influenza vaccination is recommended for kidney transplant patients, as influenza is responsible for significant morbidity and mortality in this immunocompromised population. Nevertheless, injection of influenza vaccine induces a protective immune response in only 20% to 40% of patients. Today, there are no recommendations regarding the injection time of influenza vaccine in the general population or in immunocompromised patients. In this context, recent studies conducted in healthy subjects have shown that the time of vaccination can have an impact on vaccine efficacy. This is the case for BCG, influenza, COVID-19. On this basis, we formulate the main hypothesis that the administration of influenza vaccine to kidney transplant patients would be more effective when carried out in the morning than in the evening.

Official Title
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Study of the Impact of Time of Vaccination on Response to Influenza Vaccine in Kidney Transplant Recipients -ChronoVAX

Conditions
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Vaccination; Infection

Intervention / Treatment
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* Other: Vaccine injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant patient; Follow-up at Nice University Hospital; Age > 18 years; Indication for influenza vaccination Free and informed consent; Immunosuppressive treatment including anti-calcineurin and/or Mycophenolate Mofetil (with or without corticoids). Exclusion Criteria: Known hypersensitivity to influenza vaccine or egg proteins; Influenza vaccination for the 2023-2024 season already performed; Current infection; Current acute medical condition; Treatment of rejection within the previous 3 months; Immunosuppressive therapy including CTLA4 agonist, mTOR inhibitor, complement inhibitor, anti-CD19; Polyvalent immunoglobulin infusion within the preceding 3 months; Vulnerable persons (minors, adults under guardianship or trusteeship, pregnant women, persons deprived of their liberty, persons unable to speak French); Subjects not affiliated to the Social Security system.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Morning injection<br>EFLUELDA influenza vaccine injection between 07:00 am and 09:00 am. | Other: Vaccine injection<br>* Injection of the vaccine in renal transplant patients.<br>* Other names: EFLUELDA - Fluzone High-Dose Quadrivalent;|
| Active Comparator: Evening injection<br>EFLUELDA influenza vaccine injection between 07:00 pm and 09:00 pm. | Other: Vaccine injection<br>* Injection of the vaccine in renal transplant patients.<br>* Other names: EFLUELDA - Fluzone High-Dose Quadrivalent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of antibody titer (seroconversion) 4 weeks after inactivated influenza vaccine injection in each arm. | Seroconversion will be defined as an increase in antibody titer of at least 4-fold (≥4) over pre-vaccination titer AND an antibody titer ≥ 1:40 (seroprotection) four weeks post-vaccination, for at least one of the three vaccine antigens. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of seasonal influenza virus infections in each arm. | Comparing the number of seasonal influenza virus infections in kidney transplant patients between a group of patients vaccinated in the morning and a group vaccinated in the evening. The occurrence of influenza, as confirmed by a PCR test, will be noted in the follow-up consultation. | 8 months | 
| Comparison the evolution of antibody titres reacting in each arm. | In kidney transplant patients, compare the evolution of antibody titres reacting with vaccine antigens 4 weeks after influenza vaccination between a group of patients vaccinated in the morning and a group of patients vaccinated in the evening. The titer of antibodies reacting with vaccine antigens is measured by ELISA ; | 7 months | 
| Evolution of the number of memory B cells in each arm. | To compare in kidney transplant patients the evolution of the number of memory B cells reacting with vaccine antigens 4 weeks after influenza vaccination between a group of patients vaccinated in the morning and a group of patients vaccinated in the evening. The number of memory B cells reacting with vaccine antigens will be measured by ELISPOT ; | 7 months | 
| Evolution of the number of CD4+ T cells in each arm. | Comparing the evolution of CD4+ T cells reacting with vaccine antigens in kidney transplant patients 4 weeks after influenza vaccination between a group of patients vaccinated in the morning and a group of patients vaccinated in the evening. The number of CD4+ T cells reacting with vaccine antigens will be measured by in vitro proliferation assay; | 7 months | 
| Evolution of the number of CD8+ T cells in each arm. | Comparing the evolution of CD8+ T cells reacting with vaccine antigens in kidney transplant patients 4 weeks after influenza vaccination between a group of patients vaccinated in the morning and a group of patients vaccinated in the evening. The number of CD8+ T cells reacting with vaccine antigens will be measured by in vitro proliferation assay; | 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Kidney transplant, Vaccination