Influenza is a common and potentially life threatening infection. The constant evolution
of the virus poses challenges on the cross-reactive response of the immune system, and
emergence of new strains renders the antibody-mediated protection insufficient. Cellmediated
immunity (CMI) may attenuate the severity of illness and provide better heterosubtypic
coverage. A myriad of underlying comorbidities affect the outcomes of
influenza infection; however, such known risk factors fail to explain a significant
proportion of severe influenza infections.
To investigate cross reactive antibody and cell-mediated responses and predictors of
disease severity we employed several projects and distinct cohorts- after natural infection;
live- attenuated vaccine and inactivated vaccine. The main contributions of this project
were the development of assays to measure antibody responses to multiple influenza
strains, using a microbead based assay and application of phenotypic and functional
assays to the study of influenza specific responses. Using these methods in healthy
volunteers it was shown that repeated vaccination using a recurring strain failed to elicit
increased antibody or cytotoxic T cell (CTL) responses. The administration of live
attenuated influenza vaccine (LAIV) resulted in generation of measurable cross-reactive
antibody responses. The study showed that even in a vaccine naïve adult population,
LAIV resulted in limited generation of CD4 or CD8 responses. Furthermore, the
microbead assay was applied to the study of prevalence rates of 2009 H1N1 pandemic
during the first wave, demonstrating acceptable specificity with increased sensitivity
along with the added benefits of high throughput and ability to simultaneously study
responses to multiple strains of influenza. The study of severe influenza infection during
II
the 2009 pandemic was able to characterize the profile of several pro-inflammatory
cytokines and chemokines that trended towards higher concentrations in those individuals
that succumbed to pandemic H1N1 infection. This adds to the accumulating evidence
suggesting that a cytokine storm together with inability to contain it are involved in
determining the outcome of pandemic H1N1 infection. This may potentially aid in early
identification of patients with poor prognosis and provide targets for tailored antiinflammatory
interventions. In addition the study identified, for the first time, the
association between CCR5 deletion and pandemic influenza severity, illustrating the
importance of this polymorphism beyond HIV and flaviviral infections.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:MWU.1993/23307 |
| Date | 18 February 2014 |
| Creators | Keynan, Yoav |
| Contributors | Fowke, Keith (Medical Microbiology), Coombs, Kevin (Medical Microbiology) Aoki, Fred (Pharmacology and therapeutics) Soussi Gounni, Abdel (Immunology) Zhou, Yan (University of Saskatchewan) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Detected Language | English |
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