RESEARCH THEMES
VACCINE SAFETY
In 2009, the Vaccine Safety Theme had several main areas of study:
- Create a network of sites for the rapid evaluation of the safety of influenza vaccine
- Create a network of allergists to investigate allergic issues related to influenza vaccine
- Create a network of neurologists to assess the risk of Gillian Barré syndrome associated with the influenza vaccine
- Training public health professionals in vaccine safety investigation
Plans for the 2010/11 year:
Clinical Investigation of Allergic Reactions
In fall 2009, Canada has immunized most of its population with a dose-sparing adjuvanted vaccine produced by GlaxoSmithKline (GSK). This vaccine contained monovalent A/California/7/2009 (H1N1)v-like strain (X-179A) antigen adjuvanted (AS03) with DL-α-tocopherol, squalene and polysorbate 80 (Arepanrix®). Between October 24th and December 31st 2009, many cases of anaphylaxis following the administration of the adjuvanted pH1N1 vaccine were reported to the passive surveillance system. There were also many reports of patients with clinical manifestations compatible with allergic reactions (urticaria and angioedema) or with an oculo-respiratory syndrome. Oculo-respiratory syndrome is an adverse reaction to the influenza vaccine, characterized by the presence of bilateral conjunctivitis, facial oedema and acute respiratory symptoms, including respiratory distress, sensation of throat closure, difficulty swallowing, hoarse voice, chest tightness, cough and/or wheezing. While clinical investigation has shown that ORS was not IgE mediated,1 many symptoms/signs of ORS (such as bilateral conjunctivitis, cough, wheezing, dyspnea and facial oedema) overlap those of type I hypersensitivity reactions and because these reactions occur within similar time frames (~ 40% occur ≤ 4 hours of vaccination), it remains difficult to clinically distinguish between the two entities. Notwithstanding the large number of vaccinated individuals, the observed rate of anaphylaxis, allergic reaction and ORS per 100 000 doses administered exceeds the expected number of these three types of adverse events based on surveillance in previous years.
True IgE mediated allergy or anaphylaxis to vaccines in general is exceedingly rare. Other non-IgE mediate Pathways may also produce anaphylaxis or allergic-like manifestations. Complement activation is known to induce allergic-like manifestations in a non-IgE mediated fashion. Activation of the complement system leads to the production of anaphylatoxins which trigger release of histamine from mast cells and basophils known to be associated with anaphylactic reactions. The kallikrein-kinin system is another endogenous metabolic cascade which releases bradykinin (BK). BK is a potent vasoactive molecule that causes vasodilation and capillary leakage. Most often, this cascade is triggered by the activation of the contact system. Accumulation of kinin due to overproduction or insufficient catabolism can cause angioedema.
The purpose of this protocol is to investigate what proportion of patients who reported anaphylaxis and allergic-like reactions actually had an IgE mediated allergic reaction to Arepanrix or its components, and the proportion that are allergic to the 2010-2011 trivalent inactivated seasonal influenza vaccine (TIV). In addition, we want to compare these patients to controls or to patients with ORS and estimate the proportion who have biomarkers of non-IgE pathways that can be associated with allergic-like reactions.
HCW Surveillance
The team will expand their network to seven sites and between 3000 and 10000 health care workers, with the objective of detecting a frequency of AE that would be much smaller than what could have been seen with clinical trials of patients in the hundreds. Next year, the objective will be to study the vaccinations prior to the general campaign, which would provide earlier data.
Egg Allergy
The team will repeat the study this year and next with the seasonal vaccine which has historically had more egg content. This is in order to generalize the safety data. The goal is to recruit 500 patients over two years, with controls the same size.
Neurology Network
This year, there will be activities unrelated to GBS, mostly related to anesthesia or paresthesia reported post vaccination.
Vaccine Safety Training
The Vaccine Safety group will host a workshop at the end of the Canadian Immunization Conference in December, to train epidemiologists and statisticians in doing the self-controlled case design.
Gaston De Serres MD
Principal Investigator
Bio coming soon.
