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http://hdl.handle.net/11375/27978
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DC Field | Value | Language |
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dc.contributor.advisor | Loeb, Mark | - |
dc.contributor.author | Switzer, Charlotte | - |
dc.date.accessioned | 2022-10-12T01:04:50Z | - |
dc.date.available | 2022-10-12T01:04:50Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | http://hdl.handle.net/11375/27978 | - |
dc.description.abstract | Children are at high risk for influenza-related morbidity, including severe complications of illness and hospitalizations. Seasonal influenza vaccination is recommended as the primary method of prevention and protection. Vaccine efficacy has been shown to vary based on host demographics, immune history, influenza type and subtype, and seasonal match of the vaccine antigens to the circulating influenza strains. Adjuvanted vaccination has been shown to induce greater breadth, magnitude and longevity of antibody responses. Research characterizing correlations between host factors, vaccine formulation, antibody responses and influenza outcomes would provide insight on how these relationships contribute to adjuvant-mediated vaccine effectiveness in children. In this thesis, I explored whether adjuvanted vaccination was associated with attenuated symptom severity in breakthrough influenza infections, as compared with non-adjuvanted vaccinees. I then explored the utility of vaccine reactions as predictors of post-vaccination antibody responses, accounting for the effect modification of the adjuvant. Finally, I used a causal mediation analysis to estimate the proportion of relative protection in adjuvanted vaccinees which is attributable to the increased antibody responses in this group. We found that adjuvanted vaccination was associated with significant reductions in fever and systemic symptom severity in breakthrough influenza A infections. We observed that total, systemic and respiratory reactogenicity significantly interacted with adjuvanted vaccination, leading to enhanced antibody responses relative to non-adjuvanted vaccinees. Finally, we found that adjuvanted vaccine protection was not significantly mediated by the increased antibody titers in this group. Our findings provide insight on determinants of adjuvanted vaccine effectiveness in children. Our work may inform future research examining the adjuvant moderation of innate and adaptive immunity in children, which may help define new correlates of protection against influenza. Greater understanding of the network of these relationships and their causal contribution to vaccine protection would contribute to the fields of immunology, vaccinology, and epidemiology. | en_US |
dc.language.iso | en | en_US |
dc.title | Adjuvanted Influenza Vaccination in Children | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Health Research Methodology | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
dc.description.layabstract | Children are at high risk of complications related to influenza infections, and are recommended to receive seasonal vaccination. Identifying host and vaccine characteristics which are associated with protection against influenza in children would be valuable for the development of improved vaccines. Adjuvanted influenza vaccines have been assessed in clinical trials but are not yet licensed for children. In this thesis, we evaluate relationships between vaccine formulations, reactions, the magnitude of post-vaccination antibody responses, protection against influenza and presentation of symptoms in breakthrough infections. We aim to further explore these relationships by estimating the proportion of relative adjuvanted protection which is mediated by increased antibody responses to this vaccine. We explore the relationships between vaccine formulation and host factors, and test the associations between these relationships and adjuvanted vaccine efficacy and effectiveness in children. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Switzer_Charlotte_E_2022July_PhD_Final3.pdf | 1.3 MB | Adobe PDF | View/Open |
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