Optimal timing of booster doses in a highly vaccinated population with minimal natural exposure to COVID-19

Population-level waning of protection following immunising exposures is an important determinant of susceptibility to COVID-19 outbreaks. This work outlines an individual-based model (IBM) for the transmission and clinical impact of SARS-CoV-2 that explicitly represents the immunological response to vaccination and infection of each individual. The IBM evaluates waning of immunity to inform risk of infection and related clinical outcomes across a large freely mixing population over time by age and prior exposure status. Modelling immunological responses allows us to investigate the likely impact of immune escape variants based on the landscape in which they emerge. The model described in this paper was motivated by the need to anticipate health and societal impacts of COVID-19 in Australia following emergence of the Omicron variant, in the context of high national vaccine uptake but low infection exposure. It provides a flexible framework for modelling policy-relevant scenarios to inform preparedness and response actions as immunity in a population changes through time. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by the Australian Government Department of Health and Ageing Office of Health Protection. Additional support was provided by the National Health and Medical Research Council of Australia through its Centres of Research Excellence (SPECTRUM, GNT1170960). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors