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Title: Quantifying antigenic and genetic relationships among a global panel of lyssaviruses
Author: Horton, D. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Using fluorescent antibody virus neutralisation tests, optimised for each virus, I have measured the neutralisation titres of rabbit sera against a global panel of divergent lyssaviruses. Those neutralisation titres were then used to generate antigenic maps, allowing visualisation of antigenic distances to within 1.3 two-fold dilutions in titre. Antigenic distances were compared with glycoprotein ectodomain sequence data, of which 20/30 sequences were obtained by direct sequencing as part of this study. These comparisons revealed clinically important differences between genetic and antigenic relationships. Vaccine strains and wild-type genotype 1 rabies viruses were antigenically distinct, and three of the Eurasian bat viruses were antigenically similar to known genotypes. To evaluate the validity of extrapolating animal model data to other species, I have compared the serological responses of mice, dogs, monkeys, foxes and raccoon dogs using antigenic cartography. The responses of rabbits, mice, monkeys and dogs correspond but orally vaccinated foxes and racoon dogs do not. Passive immunoglobulin treatment is a crucial part of rabies post exposure treatment, and here I have also shown that it is possible to predict the titre of polyclonal passive immunoglobulin treatments to divergent lyssaviruses. Together the results of this study show a measurable spectrum of antigenic distances between lyssaviruses that can be used for rational design of active and passive preventative treatments.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available