Past Addison Pediatric Project Details

A Prospective study Evaluating COVID-19 Vaccine immunogenicity in Organ Transplant Recipients (the PREVenT-COVID study) – Pediatric Arm extension

When the initial results from the COVID-19 vaccines showed they were upwards of 80 per cent effective in preventing serious illness and hospitalization, everyone was optimistic and excited, except for those with underlying medical conditions and their families. No one knew how well vaccines would work to protect people such as transplant recipients who are on immunosuppressant drugs to prevent rejection. There was even less data for children with organ transplants.

The PREVenT COVID study will help researchers understand how much protection (antibodies and T-cells) children with organ transplant have after vaccination and how long this protection lasts. This information will help public health officials make recommendations about additional doses of vaccines for this population. The study team will also be able to document vaccine side effects experienced by children with organ transplant. Researchers will follow approximately 40 children and youth with organ transplant from Alberta, British Columbia, and Ontario for twenty-four months from their first dose of COVID-19 vaccine.

The Government of Canada COVID-19 Immunity Task Force has funded the first year of this study. The Addison Fund for Pediatric Transplant Research is supporting the expanded second year of the project.

The objectives for Phase 2 of the PREVenT COVID-19 pediatric study are as follows:

1. Determine persistence of immune responses to authorized COVID-19 vaccines in 40 pediatric SOT recipients at 18 and 24 months after receiving first dose of vaccine.
2. Continue to assess the safety of COVID-19 vaccines in 40 pediatric SOT recipients, including documentation of rare, SOT-specific safety concerns such as rejection.
3. Determine the incidence of COVID-19 infection occurring at least 14 days after the first dose of COVID-19 vaccine and after any subsequent doses (regardless of time elapsed) in pediatric SOT recipients.

Primary Investigator: Dr. Hana Mitchell

Co-Investigators: Dr. Manish Sadarangani, Dr. Tom Blydt-Hansen, Dr. Sneha Suresh, Dr. Catherine Burton, and Dr. Allen Upton

For an up-to-date list of publications by Dr. Hana Mitchell, please see ResearchGate

 

Read more about the importance of this research to immunosuppressed transplant children and their families.

Development and validation of a novel assay to quantify alloantigen specific T cells

Following transplantation, immune cells in the recipient recognize the new organ as a foreign invader and subsequently launch an attack to destroy it. To stop this immune response, transplant recipients are placed on immune-suppressing drugs that severely reduce the immune system’s normal ability to fight off infections and cancers. It is therefore critical to prescribe just enough immune-suppressing drugs to prevent organ rejection, but not so much that patients suffer from the numerous side effects of these medications. Currently, there are no tools available to measure how well immune suppression is working in each transplant patient. Although tissue biopsies are often performed to assess whether rejection is happening or not, they are often done too late, after immune cells have already caused irreversible transplant damage.

The team intends to develop a new test that will rapidly measure immune responses to a transplant using a small amount of blood. The test is based on a fascinating immunological phenomenon whereby immune cells from the recipient that want to kill the transplanted cells pick up proteins that are exclusively expressed on the very cells they are trying to attack, allowing us to quantify the number of these killer immune cells. The team believes that by quantifying these dangerous immune cells, it will be possible to determine the risk of transplant rejection and give doctors the information they need to prevent transplant rejection and individualize immune-suppressive drug regimens to enhance transplant and patient health.

Primary Investigator: Megan Levings

Co-Investigaors: Dr. Tom Blydt-Hansen and Dr. Caroline Lamarche 

For an up-to-date list of publications by Dr. Megan Levings, please see ResearchGate

Investigating the role of metabolism in predicting outcomes in pediatric transplant patients

For children living with kidney or heart transplants, it is well known that some will develop chronic forms of rejection after the first year that limits the chance of success. Some children’s immune systems adapt better and become “tolerant” to the new organ, but the reasons for this are not entirely clear. While medications are important, a child’s metabolism can play a role, which includes things like nutrition and disease. This team will look at patient samples to see if there are changes that we can measure in metabolism that predict who will have a positive or negative response to the transplant.

Primary Investigator: Dr. Tom Blydt-Hansen

Co-Investigator: Dr. Kathryn Armstrong, Dr. Simon Urschel, and Dr. David Wishart 

For an up-to-date list of publications by Dr. Tom Blydt-Hansen, please see ResearchGate

Optimizing varicella immunization in children living with transplants to prevent disease and improve long-term health

Due to effective vaccine programs, chickenpox (or varicella) is relatively under control. However, for children living with a transplant, varicella can cause pneumonia, brain infections, and even death. Studies show that varicella vaccine is safe and effective in some transplant patients and experts developed a guideline for determining which children with organ transplants could safely get the varicella vaccine. This team will study how to use this guideline in transplant clinics to identify concerns that parents and healthcare providers have about varicella vaccination in children with transplants, and measure how the vaccine affects children’s quality of life. The results will assist physicians in determining the best way to vaccinate children with organ transplants.

Primary Investigator: Dr. Manish Sadarangani

Co-Investigators: Dr. Karina Top and Dr. Catherine Burton

For an up-to-date list of publications by Dr. Manish Sadarangani, please see ResearchGate

Preparing for Combined Stem Cell and Solid Organ Transplants: Learning from Hematopoietic Mixed Chimeras

Dr. Krueger’s team will look at how to combine a stem cell transplant with a solid organ transplant to convince the recipient’s immune system into accepting the new organ as its own. The study will examine a select population of kids from centres across Canada who have had stem cell transplants and have been able to achieve a state of tolerance to determine why some pediatric patients are able to achieve tolerance and others are not. This could potentially mean that transplant patients would no longer require immune suppression drugs, effectively turning transplant into a cure.  This project will be incorporated into the CNTRP Project 6: Improving pediatric outcomes in transplantation and the CNTRP Project 4: Strategies for immunomodulation and transplant tolerance.

The need for pediatric specific transplant research cannot be over-stated. In Canada (excluding Quebec), between 2006-2015, 1101 children had solid organ transplants. That number continues to grow exponentially every year as medical advances have made it possible for some of the sickest patients to survive. However, pediatric transplant patients are not simply small adults. They have unique needs and issues that require specific areas of study. 

Primary Investigator: Dr. Joerg Krueger

Co-Investigators: Dr. Donna Wall, Dr. Lori West, Dr. Victor Lewis, Dr. Pierre Teira, Dr. Elie Haddad, Dr. Sunil Desai, Dr. Rulan Parekh, Dr. Geoffrey Cuvelier, and Dr. Kirk Schultz 

For an up-to-date list of publications by Dr. Joerg Krueger, please see ResearchGate