The objectives of this study are to understand the long-term consequences of repeated annual influenza vaccination among healthcare workers (HCWs) and to use statistical and mathematical modelling to elucidate the immunological processes that underlie vaccination responses and their implications for vaccination effectiveness. These objectives will be achieved by pursuing three specific aims: 1. To study the immunogenicity and effectiveness of influenza vaccination by prior vaccination experience 2. To characterize immunological profiles associated with vaccination and infection 3. To evaluate the impact of immunity on vaccination effectiveness. Under Aim 1, a cohort of hospital workers will be recruited and followed for up to 4 years to assess their pre- and post-vaccination and post-season antibody responses, and their risk of influenza infection. These outcomes will be compared by vaccination experience, classified as frequently vaccinated (received ≥3 vaccines in the past 5 years), infrequently vaccinated (\<3 vaccinations in past 5 years), vaccinated once, vaccine naïve and unvaccinated. In Aim 2, intensive cellular and serological assessments will be conducted to dissect the influenza HA-reactive B cell and antibody response, and build antibody landscapes that typify the different vaccination groups. In Aim 3, the data generated in Aims 1 and 2 will be used to develop a mathematical model that considers prior infection, vaccination history, antibody kinetics, and antigenic distance to understand the effects of repeated vaccination on vaccine effectiveness. Completion of the proposed research will provide evidence to inform decisions about continued support for influenza vaccination programs among HCWs and general policies for annual influenza vaccination, as well as much needed clarity about the effects of repeated vaccination. In March-April 2020 pursuant to the SARS-CoV-2 global pandemic an administrative supplement added a SARS-CoV-2 protocol addendum for follow-up of COVID-19 infections amongst our HCW participant cohort. The following objectives were added: 1. To estimate risk factors and correlates of protection for SARS-CoV-2 infection amongst HCW 2. To characterize viral kinetics and within-host viral dynamics of SARS-CoV-2 infecting HCW 3. To characterize immunological profiles following infection by SARS-CoV-2 4. To characterize immunological profiles following vaccination for SARS-CoV-2.
Age range
18 Years – 60 Years
Sex
ALL
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Seropositivity post-vaccination (influenza vaccine)
Timeframe: Post-vaccination blood draws are at 14-21 days post vaccination. Collected each year 2020-2023 post annual influenza vaccination.
Seropositivity post-season (influenza vaccine)
Timeframe: End of the season blood draws are in October or November each year, at the conclusion of Australia's annual influenza season. Vaccination usually occurs in April or May. Collected each year 2020-2023 post annual influenza season.
Fold-rise in geometric mean antibody titre (GMT) pre- to post-vaccination
Timeframe: Changes from day 0 to day 14-21 post influenza vaccination. Collected each year 2020-2023 pre and post annual influenza vaccination.
Fold-change in geometric mean antibody titre (GMT) post-vaccination to post-season
Timeframe: Changes from day 14-21 to post-season. Influenza season in Australia is approximately May to November. Pre-vaccination to post-season is approximately April or May to October or November each year. Collected each year 2020-2023.
Seroconversion fraction post-vaccination
Timeframe: Changes from day 0 to day 14-21 post influenza vaccination. Collected each year 2020-2023 pre and post annual influenza vaccination.