Does Repeat Influenza Vaccination Constrain Influenza Immune Responses and Protection

Summary

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.

Conditions

• Influenza, Human
• SARS-CoV-2 Infection

Interventions

BIOLOGICAL

Influenza vaccination: Fluarix Tetra, Vaxigrip Tetra, Fluquadri, Fluad Quad, Afluia Quad, Flucelvax Quad

Influenza vaccine made available to healthcare workers at the participating healthcare sites, as part of their free vaccination campaigns for healthcare workers.

BIOLOGICAL

SARS-CoV-2 vaccination: Comirnaty or Vaxzevria

SARS-CoV-2 vaccine made available to healthcare workers at the participating healthcare sites, as part of their free vaccination campaigns for healthcare workers.

Sponsors & Collaborators

• The University of Queensland

  collaborator OTHER

• Sydney Children's Hospitals Network

  collaborator OTHER

• The Alfred

  collaborator OTHER

• University of Adelaide

  collaborator OTHER

• The University of Western Australia

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  collaborator OTHER

• University of Newcastle, Australia

  collaborator OTHER

• University of Melbourne

  lead OTHER

Principal Investigators

• Sheena Sullivan, MPH, PhD · University of Melbourne

• Annette Fox, PhD · University of Melbourne

• Adam Kucharski, MMath, PhD · London School of Hygiene and Tropical Medicine

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-04-02

Primary Completion

2025-06-30

Completion

2025-06-30

Countries

• Australia

Study Locations