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The Impact of Inherent Measurement Error in the Hemagglutination Inhibition Assay for the Evaluation of Vaccine Immunogenicity

dc.contributor.advisorSpieker, Andrew J
dc.contributor.advisorGreevy, Robert A
dc.creatorLee, Aaron Xian Ti
dc.date.accessioned2021-09-22T14:50:16Z
dc.date.available2021-09-22T14:50:16Z
dc.date.created2021-08
dc.date.issued2021-08-11
dc.date.submittedAugust 2021
dc.identifier.urihttp://hdl.handle.net/1803/16866
dc.description.abstractThe hemagglutination inhibition assay (HAI) is a method to evaluate the degree to which a vaccine elicits an immune response. Pre-determined dilutions (typically two-fold) of a patient’s blood serum have a fixed amount of virus added to a plate of wells. After an incubation period, red blood cells are added; after an additional incubation period, the wells can be visually evaluated. The highest serum dilution that prevents hemagglutination is taken to be the serum HAI titer, the idea being higher titers are more indicative of an immune response. This method has inherent measurement error in the sense that a patient’s true underlying titer is only observed as the maximum dilution tested that is lower than the underlying titer. The most common analytical approach to compare HAI titers involves regression analysis of log-transformed observed titers; the degree of information loss and bias resulting from discretization has not been well characterized. Simulations were conducted to assess the effect of discretizing titers, with specific emphasis on bias and efficiency. The bias shows a periodic relationship with the dilution factor. Common methods to a Phase I immunogenicity study were also applied to compare a high dose of the influenza vaccine to a standard dose in paediatric solid organ transplant patients.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.subjectHAI, vaccine, regression
dc.titleThe Impact of Inherent Measurement Error in the Hemagglutination Inhibition Assay for the Evaluation of Vaccine Immunogenicity
dc.typeThesis
dc.date.updated2021-09-22T14:50:16Z
dc.type.materialtext
thesis.degree.nameMS
thesis.degree.levelMasters
thesis.degree.disciplineBiostatistics
thesis.degree.grantorVanderbilt University Graduate School
dc.creator.orcid0000-0002-2136-7958


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