Director, Vaccine Evaluation Centre, CFRI
Professor, Pediatrics, Division of Immunology and Infectious Diseases, Department of Pediatrics, University of British Columbia
Canadian Institutes of Health Research/Wyeth Chair in Clinical Vaccine Research

Research Areas:

• Vaccines and immunization
• Epidemiology of vaccine-preventable infections
• Vaccine safety
• Immunization program evaluation

Dr. Scheifele is Director of CFRI’s Vaccine Evaluation Center (VEC), which is a leading centre for applied vaccine research in Canada. Investigators who contribute to the VEC’s research program include Dr. Simon Dobson, Dr. Jan Dutz, Dr. Julie Bettinger, Dr. Tobias Kollman, Dr. Laura Sauvé, and Mrs. Gordean Bjornson. The researchers share a field team (coordinators, nurses, assistants), data management group (manager, statistician, assistants) and specialized laboratory. The main research themes involve disease burden studies, vaccine clinical trials, and studies to fine tune public immunization programs, including ongoing assessment of vaccine safety. The VEC researchers collaborate with vaccine specialists across the country and with provincial and federal health officials, with the goal of efficiently translating new vaccine products into optimal vaccination programs for children and adults.

Dr. Scheifele is co-leader and data supervisor for the Immunization Monitoring Program, Active (IMPACT), an active surveillance program involving 12 pediatric centers across Canada. This project is funded by the Public Health Agency of Canada and operated by the Canadian Pediatric Society and its specialist members in infectious diseases. Nurse monitors at each hospital actively search for admissions with adverse events following immunization, to assess causes and outcomes. This is a key means of assessing vaccine safety, particularly the occurrence of uncommon, severe reactions. Monitors also report on selected vaccine preventable diseases, as a measure of vaccine program effectiveness. Surveillance presently includes varicella, pertussis, invasive pneumococcal, meningococcal and influenza admissions.

Dr. Scheifele plays a leading role in preparing for studies that will be necessary for a pandemic influenza vaccine. It will be important to make a vaccine available to Canadians as quickly as possible in such a crisis, but in doing so health authorities must be sure that the vaccine is safe and effective. Dosing requirements will have to be worked out for all age groups, from infants to the elderly. Safety must be carefully assessed in several thousand individuals, of all ages. Many centers will need to be involved to carry out these large studies, the logistics for which need to be carefully planned and tested at intervals. Questions that could be answered in advance of a pandemic need to be addressed and identified.

Objective
The objective of the Rapid Trials theme is to develop and test appropriate methodologies to rapidly evaluate pandemic vaccines for safety and immunogenicity in persons of all ages. With the arrival of H1N1 pandemic influenza, the objective was refined to rapidly evaluating the Canadian-made vaccine in populations at highest risk of severe infection and most likely to benefit from vaccination.

Specific aims

1. To assemble a network of trials centers with sufficient capacity to conduct large scale vaccine studies.
2. To establish the key infrastructure needed for rapid completion of trials, including means to enroll volunteers before vaccine becomes available, to deliver vaccinations within a short time and to assemble study data using a web-based electronic platform.
3. To develop the capacity to evaluate H1N1 pandemic vaccine in special populations at risk, including pregnant women and aboriginal persons.
4. To expand the capacity to evaluate immune responses to influenza viruses (vaccine and variant strains) in collaboration with the National Microbiology Laboratory (NML).
5. To explore means to streamline studies, such as innovative procedures for obtaining informed consent and use of web-based safety debriefing methods.

Research plan, methodology, outcomes and timelines
Trials of H1N1SW vaccines will be conducted over a 3-year period, following the cycle from first introduction of the new vaccine to its subsequent inclusion in trivalent seasonal vaccines as the virus subsides from pandemic to “normal” activity over 2-3 years.

PCIRN trials will usually be undertaken to provide timely information about vaccine properties. This requires early access to vaccines (as soon as available), rapid completion of the trials and prompt reporting of key observations to program providers and the general public.

Four PCIRN centers will collaborate with the Public Health Agency of Canada (PHAC) to rapidly evaluate a seasonal influenza vaccine in 300 adults during September/October 2009. This will provide timely safety and immunogenicity data about this new vaccine while serving to test the special measures required for accelerated study completion and reporting. With all 4 centers completing vaccinations during the same one week period, safety observations for days 0-6 after vaccination will be reported within 3 weeks of study initiation i.e. while public programs are still in progress.

Some PCIRN centers will collaborate with vaccine manufacturers to conduct pre-licensure trials of pandemic vaccines, including the vaccine to be distributed in Canada. These are not official PCIRN projects but they provide an important service to the public and aid government approval processes.

As the pandemic vaccine becomes available late in 2009, all 10 PCIRN trials centers will collaborate in several simultaneous studies to rapidly evaluate safety and immune responses. These studies will include:
 

1. age groups in the general population at high risk of severe influenza, including children and younger adults (some with underlying health conditions that predispose to severe outcomes)
2. pregnant women
3. aboriginal children and adults, including First Nations and Métis volunteers, some with health conditions.

Subsequent studies in Year 1 will need to examine the duration of immune responses to vaccination, the effectiveness of vaccine-induced responses against the evolving pandemic virus and the need for and response to re-vaccination. Interactions between vaccinations with pandemic and seasonal strains will require study.

Studies in Years 2 and 3 will evaluate revised trivalent seasonal vaccines containing the evolved H1N1SW strain. These might include new formulations with adjuvants if experience with adjuvanted pandemic vaccines is encouraging. Study methodology will be revised progressively to take advantage of validated means to accelerate study completion.

A particular focus in Year 3 will be to define the core infrastructure that will need to be maintained for ongoing readiness to cope with an infectious diseases outbreak or pandemic, such as the minimum number of trials centers, data management centers and support laboratories needed for an optimal response.