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Does Repeated Influenza Vaccination Constrain Influenza Immune Responses and Protection?

Investigators: Christopher Blyth

Summary

This research will define influenza exposures and cellular and molecular processes that contribute to attenuating vaccine antibody responses. This in turn will inform measures to improve vaccine effectiveness, including, for example, the potential utility of adapting annual strain selection, annual recommendations for which vaccine formulations to use, vaccination schedules, and investment decisions for novel types of influenza vaccines. The outputs of our cohort surveillance will be used to inform new mathematical models of vaccination and infection dynamics relevant to this frequently vaccinated population. Health Care Workers (HCWs) represent a target group for vaccination largely comprised of healthy adults (i.e. the group for whom we believe the vaccine should work best) and who may have higher influenza infection rates. This cohort also provides opportunity to increase our understanding of the epidemiological, virological and immunological characteristics of SARS-CoV-2 infections in HCWs.

Project description

Influenza vaccines require annual re-administration both because circulating strains, especially influenza A(H3N2) viruses, undergo rapid antigenic drift demanding re-configuration of the vaccine, and because vaccine-induced immunity against homologous strains may wane. Annual seasonal influenza vaccination is currently recommended for healthcare workers (HCW) to protect themselves against infection, reduce absenteeism and minimize the risk of transmission to patients. The effects of repeated vaccination are unclear and may reduce effectiveness. This work will establish a longitudinal cohort of healthcare workers (HCW) to understand why immunogenicity and effectiveness appear to attenuate with repeated administration of the influenza vaccine. To do this, we will focus on three specific aims:

  1. To study how the immunogenicity and effectiveness of influenza vaccination is influenced by prior vaccination experience.
  2. To characterize immunological profiles following infection and vaccination
  3. To evaluate the impact of immunological profiles on vaccination effectiveness

To understand how individual-level antibody responses influence infection risk, and hence the effectiveness of vaccination, it is necessary to combine estimates of immunity with models of exposure risk. To account for such heterogeneity in infection, we will combine all our data, including surveillance and serological data, to infer individual-level infection risk for a given immunological profile and prior exposure history, and hence evaluate the potential impact of different vaccination strategies.

Given the similarities between cases presenting with influenza and cases presenting with COVID-19, additional surveillance activities will leverage the existing cohort to improve our understanding of the epidemiology of the COVID-19 epidemic, the immunological responses to SARS-CoV-2 infection and further understand the virological characteristics.

External collaborators: A/Prof Sheena Sullivan, Dr Annette Fox, A/Prof Adam Kucharski, Prof Kanta Subbarao, Prof Helen Marshall, A/Prof Julia Clark, Prof Allen Cheng, Prof Peter Wark, Prof Kristine Macartney, Vivian Leung, Louise Carolan, Jasminka Sterjovski, Dr Craig Dalton

Funders: National Institutes of Health