Natural immune boosting can cause synchrony in susceptibility and outbreaks of respiratory infections with rapidly waning immunity

Natural immune boosting is a mechanism in which re-exposure to a pathogen while immunity is waning can prolong protection against reinfection. Its role in viral respiratory-tract infections with rapidly waning immunity has not been studied in mathematical models. Here we use a deterministic compartmental model to investigate the effect of immune boosting on such infections, and how the reduction in transmission due to non-pharmaceutical interventions during the covid-19 pandemic could affect immune waning and boosting. We find that immune boosting can introduce unstable equilibria into the model, and we show in simulations that this can amplify, or even cause, oscillations in infections and disease outbreaks. After periods of reduced transmissibility, representing non-pharmaceutical interventions, simulations with more immune boosting exhibit larger rebound outbreaks that occurred sooner. Observed incidence of respiratory syncytial virus infection in Scotland between 2016 and 2023 can be equally explained by models with high levels of immune boosting, and models without natural immune boosting. To produce the same incidence, models with more immune boosting require a greater mean transmissibility, suggesting that models underestimating natural immune boosting will also underestimate transmissibility. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (200907), a partnership between the United Kingdom Health Security Agency (UKHSA), the University of Liverpool, the University of Oxford and the Liverpool School of Tropical Medicine. The views expressed are those of the authors and not necessarily those of the NIHR, the UKHSA or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data used in this analysis were released by Public Health Scotland under the Open Government Licence for public sector information, https://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/ available at https://www.opendat a.nhs.scot/dataset/48a9310e-4db3-44a4-bce8-6b4be9deb88a/resource/3 7beac86- f8fb- 4ab5- 9457- 2b8ddac9c089/download/respiratory_scot.csv 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 Code and data to reproduce this analysis are available at https://github.com/markgpritchard/ImmuneBoostingODEs