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Title: Strategies for influenza vaccines
Author: Hartgroves, Lorian Cedar Safir
ISNI:       0000 0004 2682 1886
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
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The high mutation rate of influenza virus results in antigenic drift, meaning that each of the three components in the trivalent influenza vaccine are updated regularly so that the vaccine antigen closely matches the predominant or emerging strain. The production of influenza vaccines from the chosen seed has relied on embryonated chickens eggs for more than 40 years. Recent technological advances have resulted in the evaluation of several cell lines as alternative substrates for influenza vaccine production. Reverse genetics of influenza viruses allows the creation of viruses at will from cDNA. However, licensed cell lines have so far proved unpermissive for virus rescue and permissive lines remain largely unlicensed. A reverse genetics system for the production of influenza vaccines in PER.C6 cells has been developed and optimised. Many recent clinical isolates do not grow in eggs and hence require reassortment with a high growth, egg permissive backbone. Adventitious agents aside, cell lines able to support growth of clinical isolates could be used directly included in the vaccine, without the need for reassortment. However, this could lead to year on year variation in the quality and characteristics of the vaccine. Particularly pertinent, is the variation in the amount of IFN a clinical isolate can induce, which could severely limit yields. Yields and effects of IFN for a panel of high and low inducing viruses are investigated in a number of potential vaccine cell lines. The mechanisms behind virus IFN induction have been investigated. Using a panel of high and low inducing viruses the differences in growth and viral protein expressions, and activation of PRR has been analysed. The IFN response in PER.C6 cells has been characterised. Through an improved understanding of the mechanisms of IFN induction and inhibition, antagonists could be introduced into the vaccine cell line to improve yields.
Supervisor: Barclay, Wendy Sponsor: Sanofi Pasteur
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral