In short
Mumps is a childhood disease, caused by the mumps virus. Nowadays, however, it mostly affects young adults who have been vaccinated with the trivalent MMR vaccine (Mumps-Measles-Rubella). There have been multiple mumps outbreaks around the world, including one in 2012 in Belgium. This PhD project focuses on why these outbreaks reoccur.
Project description
The recent outbreaks of mumps and the increasing age of the affected populations necessitate research into the causes of the failure of the current vaccine strategy. To decide whether the current vaccine should be updated or vaccine strategies need adjustment, the exact nature of the vaccine failure has to be defined. In one first scenario, decreasing homology between the vaccine strain (isolated from a patient in the USA in 1963) and circulating strains may have resulted in antibodies that have a lower cross-neutralizing capacity towards the current circulating strains (primary vaccine failure). This can be solved by either using a new, up-to-date, vaccine strain or by formulating a vaccine that is composed of several mumps genotypes. In another scenario, faster waning of the immune response (secondary vaccine failure), rather requires a third vaccine dose, 5 to 10 years after the second dose and even later doses might be required to avoid later infection waves.
To determine which mechanisms are at play, the sequence variation of the major mumps virus proteins of virus isolates and vaccine strains have been studied in the context of their 3D structure. Because HN and F are the key antibody target sites, special attention was be given to the variation within the epitopes of these proteins. We also examined variation in putative T cell epitopes in external and internal antigens. Moreover, we analyzed whether sequence variation can be correlated with the early onset of waning immunity and whether viral interference might be an alternative for the relative underperformance of the mumps component in the MMR vaccine.
The objectives of this project were:
- To examine to what extent both vaccine and outbreak strains compare and differ in their B cell epitope profile based on in silico predictions.
- To correlate the in silico and wet lab results for B cell epitopes with cross-protective humoral immunity in the Belgian population. To examine whether there is a functional difference in seroneutralisation titers of vaccinated people against the homologous and heterologous strains at different ages. To assess whether or not this can sufficiently explain the breakthrough infections in vaccinated people.
- To what extent both vaccine and outbreak strains compare and differ in their T cell epitope profile based on in silico predictions.
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