Comparison of High vs. Standard Dose Influenza Vaccines in Adult Solid Organ Transplant Recipients

Principal Investigators: Natasha Halasa, MD , MPH (Main PI), Abhijit (Ajit) Limaye, MD (Site PI), Cynthia Fisher, MD (Co-I)

Sponsors: National Institute of Health, Vanderbilt University

Study Design: Phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial

This phase 2 multi-center, randomized, double-blind study compares three different flu vaccine regimens in adult solid organ transplant recipients, to understand vaccine strategies and immune responses and better guide vaccine recommendations in the early post-transplant period.

Status: Currently, in its third year of enrollment, the study targets to enroll approximately 396 subjects as new participants over a four year period at all five sites. At the University of Washington, there are more than 65 patients enrolled in the study.

Study Sites

Comparison of High Dose vs Standard Dose Influenza Vaccines in Lung Allograft Recipients

Lung transplantation is a life-saving therapy for patients with advanced lung disease and is associated with an improvement in quality of life. However, due to the need for life-long immunosuppression to prevent acute cellular rejection and chronic lung allograft dysfunction (“chronic rejection”), lung transplant recipients are at risk for developing major infections. Hence, the influenza vaccine is strongly recommended for this population. However, due to the effects of immunosuppression, the immune responses from the vaccine are significantly impaired in these recipients.

This phase II, multicenter, randomized, double-blind trial assesses the impact of two doses of High Dose- QIV compared to two doses of Standard Dose QIV in lung allograft recipients who are within the first three years post transplant.

Currently in its first year of enrollment, this study targets to enroll approximately 270 subjects over at least a three-year period at all five sites.

This proposed study is designed to address four key knowledge gaps:

  1.   What is the optimal influenza vaccine strategy for lung allograft recipients who are within their first three years post-transplant?

  2.  Is there increased immunogenicity with administration of two doses of HD-QIV compared to two doses of SD-QIV in the same season?

  3.  What is the durability of the humoral and cellular immunologic response at six months post-vaccination and does two doses of HD-QIV maintain higher titers compared to two doses of SD-QIV?

  4. Will the optimal immunogenic vaccination strategy be associated with an acceptable safety profile, including local and systemic reactions, and free of increased allosensitization (both humoral and cell-mediated)?

Background

Due to the intense induction and maintenance of immunosuppression in SOT recipients, the protective immune response from the influenza vaccine is significantly impaired. Despite vaccination remaining the primary strategy to prevent influenza infection and reduce influenza-associated complications, these protective immune responses are often significantly impaired in SOT recipients, especially in those who receive influenza immunization early post-transplant when induction and maintenance immunosuppression is generally more intense. Spearheaded by Vanderbilt University Medical Center and initiated by the National Institute of Health (NIH) in 2019, the Adult Solid Organ Transplant (ASOT) Study is a randomized, double-blind clinical trial that evaluates the immune response of transplant patients by comparing different flu vaccine regimen to determine the best influenza vaccine strategy in this population.

Rationale

Strategies to reduce severe influenza disease in this highly susceptible population are critical, especially since these individuals respond poorly to SD-IIV.

This proposed study was designed to address four key knowledge gaps:

  1. What is the optimal influenza vaccine strategy for adult SOT recipients, especially in the early post-transplantation period?

  2. Is there increased immunogenicity with administration of one dose of HD-IIV or two doses of HD-IIV compared to two doses of SD-IIV in the same season?

  3. What is the durability of the humoral and cellular immunologic response at six months post-vaccination and does one or two doses of HD-IIV maintain higher titers compared to two doses SD-IIV?

  4. Will the optimal immunogenic vaccination strategy be associated with increased safety risk?

The results of this proposed clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD vs. SD) and immune responses in adult SOT recipients and will guide vaccine recommendations in the early post-transplant period. Additionally, the findings of this study are likely to provide insights into optimizing vaccine strategies in a broad range of other immunocompromised populations.

Study Design

The study is a phase II, multi-center, double-blind, randomized controlled immunogenicity and safety trial comparing one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV in adult SOT recipients over at least three influenza seasons. At study enrollment, following consent, subjects will be randomized into one of three groups. Group 1 will receive two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen). Group 2 will receive two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen). Group 3 will receive one dose of HD-QIV followed by a placebo dose. compares one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV in adult SOT recipients over at least three influenza seasons. The target population is heart, kidney, and/or liver patients who are between ≥1 month and <12 months post-transplant.

Primary Objectives

Immunogenicity:

  • To compare the HAI GMT to influenza A antigens in adult SOT recipients after receiving either one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV over one influenza season.

 Safety:

  • To compare the frequency and severity of solicited local injection site adverse events (e.g. pain/ tenderness, redness, and swelling/Induration at injection site) in adult SOT recipients after receiving either one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV over one influenza season.

  • To compare the frequency and severity of solicited systemic adverse events (e.g. fevers, headache, fatigue/malaise, nausea, body ache/myalgia, general activity level, and vomiting) in adult SOT recipients after receiving either one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV over one influenza season

Secondary Objectives

Immunogenicity

  • To compare the HAI GMT to influenza B antigens in adult SOT recipients after receiving either one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV over one influenza season.

  • To compare the frequency of seroconversion (achieving a ≥4-fold rise in HAI titer) or seroprotection (presence of ≥1:40 HAI titer) in adult SOT recipients after receiving either one dose of HD-QIV, two doses of SD-QIV, or two doses of HD-QIV over one influenza season.

Vanderbilt University Medical Center

University of Washington Medical Center

Northwestern University Feinberg School of Medicine

Duke University Medical Center

University Hospital, University of Alabama, Birmingham