Does Repeat Influenza Vaccination Constrain Influenza Immune Responses and Protection

NCT05110911 | Active Not Recruiting

• 1 other identifier: 1R01AI41534
• Study Type: observational
• Target: 1,500
• Locations: 1 country
• Sites: 6

Brief 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. 1.To study the immunogenicity and effectiveness of influenza vaccination by prior vaccination experience
2. 2.To characterize immunological profiles associated with vaccination and infection
3. 3.To evaluate the impact of immunity on vaccination effectiveness.
4. 4.To estimate risk factors and correlates of protection for SARS-CoV-2 infection amongst HCW
5. 5.To characterize viral kinetics and within-host viral dynamics of SARS-CoV-2 infecting HCW
6. 6.To characterize immunological profiles following infection by SARS-CoV-2
7. 7.To characterize immunological profiles following vaccination for SARS-CoV-2.

Conditions

Influenza, Human; SARS-CoV-2 Infection

Keywords

Vaccine Response Impaired; Influenza, Human; Health Personnel; Influenza Vaccines; SARS-CoV-2 Infection; Immunologic Memory; Vaccination

Outcome Measures

Primary Outcomes (5)

• Seropositivity post-vaccination (influenza vaccine)

  Seropositivity among vaccination groups will be calculated and compared using logistic regression, with seropositivity coded as 1 if the titre ≥40, and 0 if the titre is \<40. We will test for trend among vaccination groups, assuming seropositivity will be lowest in the most highly vaccinated.

  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)

  Seropositivity among vaccination groups will be calculated and compared using logistic regression, with seropositivity coded as 1 if the titre ≥40, and 0 if the titre is \<40. We will test for trend among vaccination groups, assuming seropositivity will be lowest in the most highly vaccinated.

  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

  The changes in GMT from pre- to post-vaccination. Seroconversion is defined as samples with 4-fold increases in hemagglutination inhibition (HI) titre.

  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

  The changes in GMT from post-vaccination to post-season.

  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

  The proportion of samples with 4-fold increases in hemagglutination inhibition (HI) titre. Seroconversion post-vaccination will be calculated and compared among vaccination groups by logistic regression, with seroconversion coded as 1 if the fold-rise in titre is ≥4 and 0 if the fold-rise in titre is \<4. We will test for trend, assuming seroconversion will be lowest in the most highly vaccinated.

  Changes from day 0 to day 14-21 post influenza vaccination. Collected each year 2020-2023 pre and post annual influenza vaccination.

Secondary Outcomes (24)

• Healthcare workers (HCWs) PCR-positive for influenza at the end of each season

  Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.

• Influenza attack rate at the end of each season

  Person-time at risk, during influenza season. Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.

• Vaccine efficacy (VE)

  Person-time at risk, during influenza season. Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.

• Duration of illness (influenza)

  Days ill, during influenza season. Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.

• Haemagglutinin (HA) antibody landscapes for vaccine-naïve and highly-vaccinated healthcare workers (HCWs)

  Bloods on day 0, day 7, day 14-21 post influenza vaccination and end of season. Collected each year 2020-2023 pre and post annual influenza vaccination and end of influenza season.

Study Arms (1)

Healthcare Workers

Eligible participants will be recruited from 1 of 6 participating hospitals in Australia and will meet the following criteria: personnel (including staff, honorary staff, students and volunteers) located at a participating hospital or healthcare service at the time of recruitment who would be eligible for the hospital's free vaccination programme; be aged ≥18 years old and ≤60 years old; have a mobile phone that can receive and send SMS messages; willing and able to provide blood samples; available for follow-up over the next 7 months; able and willing to complete the informed consent process. There are no restrictions on the type of healthcare worker (HCW) that can be recruited into the study in terms of their job role. HCW will be any hospital staff, including clinical, research, administrative and support staff.

Biological: Influenza vaccination: Fluarix Tetra, Vaxigrip Tetra, Fluquadri, Fluad Quad, Afluia Quad, Flucelvax Quad; Biological: SARS-CoV-2 vaccination: Comirnaty or Vaxzevria

Interventions

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

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

Healthcare Workers

SARS-CoV-2 vaccination: Comirnaty or Vaxzevria BIOLOGICAL

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

Healthcare Workers

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Healthcare workers (including staff, honorary staff, students and volunteers) from six participating hospitals (or healthcare services) who are eligible for the hospitals' free vaccination programmes, at the time of recruitment.

You may qualify if:

• Eligible participants will be recruited from 1 of 6 participating hospitals and will meet the following criteria:
• Personnel (including staff, honorary staff, students and volunteers) located at a participating hospital or healthcare service at the time of recruitment who would be eligible for the hospital's free vaccination programme
• Be aged ≥18 years old and ≤60 years old;
• Have a mobile phone that can receive and send SMS messages;
• Willing and able to provide blood samples;
• Available for follow-up over the next 7 months;
• Able and willing to complete the informed consent process.
• There are no restrictions on the type of healthcare worker (HCW) that can be recruited into the study in terms of their job role. HCWs can be any hospital staff, including clinical, research, administrative and support staff.

You may not qualify if:

• Immunosuppressive treatment (including systemic corticosteroids) within the past 6 months;
• Personnel for whom vaccination is contraindicated at the time of recruitment.

Sponsors & Collaborators

• University of Melbourne: lead
• The University of Queensland: collaborator
• Sydney Children's Hospitals Network: collaborator
• The Alfred: collaborator
• University of Adelaide: collaborator
• The University of Western Australia: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• University of Newcastle, Australia: collaborator

Study Sites (6)

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Queensland Children's Hospital

Brisbane, Queensland, 4101, Australia

Location

Women's and Children's Hospital

Adelaide, South Australia, 5006, Australia

Location

The Alfred

Melbourne, Victoria, 3004, Australia

Location

Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• Liu Y, Sanchez-Ovando S, Carolan L, Dowson L, Khvorov A, Jessica Hadiprodjo A, Tseng YY, Delahunty C, Khatami A, Macnish M, Dougherty S, Hagenauer M, Riley KE, Jadhav A, Harvey J, Kaiser M, Mathew S, Hodgson D, Leung V, Subbarao K, Cheng AC, Macartney K, Koirala A, Marshall H, Clark J, Blyth CC, Wark P, Kucharski AJ, Sullivan SG, Fox A. Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines. Vaccine. 2023 Nov 22;41(48):7192-7200. doi: 10.1016/j.vaccine.2023.10.034. Epub 2023 Oct 28.

  PMID: 37903679 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

This study will not generate human genomic data. However, all virus sequencing data generated will be uploaded to the Global Initiative on Sharing All Influenza Data (GISAID) website, as part of standard surveillance practices of the WHO Collaborating Centre for Reference and Research on Influenza.

MeSH Terms

Conditions

Influenza, Human; COVID-19

Interventions

ChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Lung Diseases

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines

Study Officials

• Sheena Sullivan, MPH, PhD

  University of Melbourne

  PRINCIPAL INVESTIGATOR

• Annette Fox, PhD

  University of Melbourne

  PRINCIPAL INVESTIGATOR

• Adam Kucharski, MMath, PhD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 8, 2021
• Study Start: April 2, 2020
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be available after publication of results, likely in late-2024.
• Access Criteria: Data will only be shared with new collaborators under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Locations

AU (6)