The impact of rotavirus vaccine introduction on circulating wild-type rotavirus strains in Australia

Rotavirus is the major cause of gastroenteritis in children. The Rotarix® and RotaTeq® vaccines were introduced into the Australian National Immunisation Program in 2007. Rotavirus strains evolve rapidly via numerous mechanisms and vaccine introduction is likely to increase the immune pressure on wild-type strainRotavirus is the major cause of gastroenteritis in children. The Rotarix® and RotaTeq® vaccines were introduced into the Australian National Immunisation Program in 2007. Rotavirus strains evolve rapidly via numerous mechanisms and vaccine introduction is likely to increase the immune pressure on wild-type strains. This dissertation aimed to investigate the impact of vaccine introduction on wild-type rotavirus strains in Australia. Between 2007 and 2010, 13 infants with gastroenteritis were identified excreting RotaTeq® vaccine strains following vaccination. Sequence analysis revealed the G1P[5] and G6P[8] vaccine component strains underwent reassortment, resulting in vaccinederived G1P[8] double-reassortant strains. Outbreaks of rotavirus disease have continued to occur in Indigenous communities despite Rotarix® introduction. Whole genome characterisation of G2P[4] and G1P[8] outbreak strains revealed several genetic alterations which may have assisted these strains to rapidly disseminate and cause disease. Rare genotypes have been detected at an increased rate in the vaccine-era. Whole genome sequencing of a G10P[14] strain identified in the Northern Territory revealed an artiodactyl-like genome constellation. This strain may have emerged from the feral animal population in the region. A G3P[14] strain was identified in a 12 year old child, whole genome sequencing suggested the strain was derived from multiple reassortment events between strains originating in numerous species. Herd immunity in the vaccine-era may act as a selective force, changing the landscape of rotavirus strains circulating in the community. G2P[4] strains emerging in RotaTeq® states during the 2010–2011 surveillance period may reflect such an event; genetic and antigenic analysis revealed strains distinct to the G2P[5] RotaTeq® component strain. In conclusion, vaccine introduction may have impacted wild-type rotavirus strains circulating in the community. The studies in this dissertation highlight the complex nature of rotavirus epidemiology. Long-term surveillance in the vaccine-era is required to determine the impact of vaccine introduction and ensure sustained vaccine efficacy.s. This dissertation aimed to investigate the impact of vaccine introduction on wild-type rotavirus strains in Australia. Between 2007 and 2010, 13 infants with gastroenteritis were identified excreting RotaTeq® vaccine strains following vaccination. Sequence analysis revealed the G1P[5] and G6P[8] vaccine component strains underwent reassortment, resulting in vaccinederived G1P[8] double-reassortant strains. Outbreaks of rotavirus disease have continued to occur in Indigenous communities despite Rotarix® introduction. Whole genome characterisation of G2P[4] and G1P[8] outbreak strains revealed several genetic alterations which may have assisted these strains to rapidly disseminate and cause disease. Rare genotypes have been detected at an increased rate in the vaccine-era. Whole genome sequencing of a G10P[14] strain identified in the Northern Territory revealed an artiodactyl-like genome constellation. This strain may have emerged from the feral animal population in the region. A G3P[14] strain was identified in a 12 year old child, whole genome sequencing suggested the strain was derived from multiple reassortment events between strains originating in numerous species. Herd immunity in the vaccine-era may act as a selective force, changing the landscape of rotavirus strains circulating in the community. G2P[4] strains emerging in RotaTeq® states during the 2010–2011 surveillance period may reflect such an event; genetic and antigenic analysis revealed strains distinct to the G2P[5] RotaTeq® component strain. In conclusion, vaccine introduction may have impacted wild-type rotavirus strains circulating in the community. The studies in this dissertation highlight the complex nature of rotavirus epidemiology. Long-term surveillance in the vaccine-era is required to determine the impact of vaccine introduction and ensure sustained vaccine efficacy.

Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Life Sciences, Faculty of Science, Technology and Engineering, La Trobe University, Bundoora.

Thesis with publications.

This thesis was a recipient of the Nancy Millis Award for theses of exceptional merit.