RESEARCH THEMES
RAPID TRIALS
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 onset of the global Pandemic in Year 1 of the network's three-year plan, PCIRN was presented with a number of hurtles. Of particular note, PCIRN's Rapid Trials team was challenged with the inability to conduct pre-licensure studies as it had originally planned, due to time constraints and the early release of the vaccine. Nonetheless, Year 1 saw several notable successes from the team, including the impressive completion of four clinical trials, and the delivery of some very valuable information to the public health process.
The RT-02 study (Aboriginal Adults) determined that there were no apparent differences between aboriginal response to vaccine and non-aboriginal response. In fact , subjects responded robustly, exceeding responses of non-aboriginal adults in the parallel PCIRN study of same design. The RT-03 (Pediatric) study showed that one pediatric dose of adjuvanted pH1N1 vaccine elicited potentially protective titers (≥ 40) in 80% of seronegative children while a second dose raised this to 100% and increased GMT by 10-fold. Naturally primed children had strong responses; such high titers may afford greater or longer-lasting protection.In the RT-04 (Adult) study, there was no apparent effect on compatibility with TIV and H1N1 vaccine. In RT-05 (HIV-infected Adults) the protective levels were substantially increased compared with non-adjuvanted seasonal influenza vaccines.
For Year 2, the RT theme conducted two pre-release trials in truly rapid fashion.
"Our Year 2 plan represents a giant step forward in pandemic preparedness by developing means to access vaccine before licensure, and to thereby derive rapid safety data," explains Dr. David Scheifele, PI. "Earlier results can better inform program decisions, with added credibility of independent data; these collaborations will be a first in Canada, creating an important precedent for the future."
Both of this year's clinical trials, RT-06 (Adults), and RT-07 (Pediatric) worked to assess the safety of seasonal influenza vaccination in subjects who had the adjuvanted H1N1 vaccine last year, and to measure residual immunity to the H1N1 virus and immune responses to the seasonal vaccine. Both studies were carried out before the new vaccine was released for general use to provide an accurate picture of vaccine safety and responses for other Canadians.
David Scheifele MD
Principal Investigator
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.
