Molecular analysis of three Canadian Mumps outbreaks in mainly vaccinated populations

• Main Author: Frost, Jasmine
• Other Authors: Ball, Blake (Medical Microbiology and Infectious Diseases), Arsenio, Janilyn (Immunology), van Domselaar, Gary (Medical Microbiology and Infectious Diseases), Ward, Brian (McGill University), Severini, Alberto
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: 2023
• Subjects: Mumps; Phylogenetics; Whole Genome Sequencing; Virology; Newfoundland
• Online Access: http://hdl.handle.net/1993/37468

The introduction of the Measles, Mumps, and Rubella (MMR) vaccine to Canada in 1983 successfully eradicated measles and rubella, though the mumps virus (MuV) continues to persist. Recently an increase in mumps outbreaks due to genotype G mumps infections was observed in vaccinated young adult populations. Characteristics of the mumps outbreaks in Canada were explored using data from outbreaks in Manitoba, Newfoundland, and Nova Scotia. A new method of whole genome sequencing (WGS) using the pull-down of mumps-specific sequences was developed that allows for direct sequencing from clinical samples with a success rate over 70%. This method obtained 299 whole genome sequences from provincial outbreaks that were analyzed using Bayesian Evolutionary Analysis by Sampling Trees. Several conclusions can be reached from this analysis: i) WGS is a superior method to resolve and explore mumps outbreaks when compared to traditional SH gene sequencing; ii) The outbreaks are due to the endemic circulation of mumps in Canada; iii) endemic circulation of mumps likely occurs freely within both Canada and the USA. Using epidemiological data available for Manitoba, it was determined that the risk of being infected with a mumps strain that contained a non-synonymous mutation compared to a mumps genotype G consensus was eight times higher in those who only had one dose of an MMR vaccine. This suggests some single nucleotide variants might be linked to vaccine escape factors. A cross-reactivity study was conducted between the vaccine strain (genotype A) and the circulating strain (genotype G) to investigate potential reasons for waning vaccine immunity. The study used convalescent sera from mumps cases in vaccinated or unvaccinated individuals and vaccinated individuals with no mumps history. Multiple approaches were employed, including western blot, ELISA, and an attempt at Plaque Reduction Neutralization Test. The overall results were inconsistent, possibly due to a lack of cross-reactivity or variations in individual IgG immune ...