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Influenza vaccinology and clinical assessment

Lillie, Patrick (2014) Influenza vaccinology and clinical assessment. PhD thesis, University of Sheffield.

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Abstract

Influenza virus infection is a global health problem, causing both seasonal epidemics and episodic pandemics of influenza A which are associated with significant mortality and morbidity. The development of influenza vaccines stimulating protection against both antigenically drifted seasonal virus as well as new pandemic antigenically shifted virus would be a major advance. A vaccine that stimulates cellular immunity to conserved viral antigens is a potential area of interest, and could generate heterosubtypic immunity. I have been the lead clinician for both phase I and II studies of thenovel viral vectored vaccine MVA-NP+M1 (modified vaccinia virus Ankarra, expressing nucleoprotein and matrix protein 1), designed to induce cellular immunity to influenza A virus. In this role I have been involved in the design, ethical and regulatory approval of phase I studies of safety and immunogenicity of MVA-NP+M1, as well as recruiting and vaccinating volunteers. The phase I studies showed that the vaccine was safe and immunogenic in both young and elderly volunteers. In addition to my clinical role in the phase I studies, I performed laboratory based immunological assays of immunogenicity (ELISPOT testing) in both phase I and II studies. For the phase II study, I lead the safety challenge study as well as collecting, analysing and writing up the data from the quarantine challenge study. This phase II study showed that MVA-NP+M1 is partially protective against influenza challenge in healthy volunteers, that the challenge model to assess protection is safe and that further challenge studies are warranted. I have also initiated two separate clinical studies on influenza, one comparing early clinical features of influenza with those of malaria, both from volunteer challenge studies, while the other study was of the clinical assessment of severity of influenza during a busy winter influenza season, with particular reference to those patients requiring critical care. For both studies I conceived the idea, organised the data collection and analysed the data. These data are of use in pandemic settings in allowing the assessment of patients with influenza and in determining the appropriate setting for their care.

Item Type: Thesis (PhD)
Additional Information: PhD by publication
Keywords: Influenza Vaccines T-cells MVA-NP+M1 Severity assessment
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Identification Number/EthosID: uk.bl.ethos.619110
Depositing User: Dr Patrick Lillie
Date Deposited: 22 Sep 2014 11:00
Last Modified: 21 Jun 2018 09:53
URI: http://etheses.whiterose.ac.uk/id/eprint/6949

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