Influenza Vaccine Elicited Immune Response in Immunocompromised Patients (FluVacc)

March 25, 2025 updated by: Insel Gruppe AG, University Hospital Bern
This study aims to understand how well influenza vaccines work in some individuals with weakened immune systems compared to healthy individuals. Some people, such as those with HIV, multiple sclerosis, certain cancers, or autoimmune conditions, have more severe influenza disease courses due to their medical treatments. These individuals may also respond less effectively to vaccines. By comparing immune responses to the influenza vaccine in both immunocompromised patients and healthy participants, this study aims to identify patterns in vaccine effectiveness and side effects. The goal is to find better ways to predict vaccine response in vulnerable patients and improve protection against influenza.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study is a single-center, prospective cohort study evaluating influenza vaccine responses in adults with weakened immune systems compared to healthy adults. Immunocompromised participants include individuals with HIV, multiple sclerosis, rheumatological diseases, and B-cell malignancies after CAR-T cell therapy. All participants will receive a standard influenza vaccine, as recommended in Switzerland, with immune response measured through blood tests at specific time points before and after vaccination.

The primary objective is to compare influenza vaccine antibody levels in immunocompromised and healthy participants to determine if immune responses are different in the former group. Secondary objectives include examining vaccine-induced immune cell activity, side effects, and the immune profile before vaccination in each patient subgroup. The study will also analyze gut microbiome differences between responders and non-responders and develop prediction models for vaccine effectiveness based on immune and demographic data. By doing so, researchers hope to enhance the understanding of how best to protect immunocompromised patients against influenza.

Study Type

Observational

Enrollment (Actual)

147

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Universitsy Hospital Bern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Adult (≥ 18 years old) patients with immunocuppression (Patients with B-cell malignancies after CAR-T cell therapy, multiple sclerosis on sphingosin-1 modulator therapy, rheumatological diseases on methotrexate therapy or people living with HIV on antiretroviral therapy) and non-immunocompromised participants as control group.

Description

Inclusion Criteria:

  • ≥ 18 years old
  • Diagnosed with rheumatological diseases on immunosuppressive therapies, or Multiple sclerosis on immune modulating therapies, or B-cell malignancies after CAR-T cell therapy, or o PLWH with CD4 cell count >200/ul, or Non-immunocompromised individuals attending the University Clinic for Infectious Diseases to receive influenza vaccination.
  • Provided written informed consent.

Exclusion Criteria:

  • For People Living With HIV: untreated or ≥2 measured viral loads above 50cp/ml in preceding 6 months
  • For non-immunocompromised controls: any inborn or acquired condition resulting in immunosuppression.
  • Receiving B-cell depleting therapies in last 12 Months for MS, RA patients and PLWH
  • Receipt of Immunoglobulin-therapy (IVIG) ≤4 months prior to the drawing of study samples
  • < 18 years old
  • Lack of written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control Group
Non-immunocompromised controls
Biological: Influenza vaccine
Standard, commercially available, quadrivalent split-vaccine against influenza is given to all study participants.
CAR-T Cell Recipients
Patients with B-cell malignancies receiving anti-CD19 CAR T-cell therapies
Biological: Influenza vaccine
Standard, commercially available, quadrivalent split-vaccine against influenza is given to all study participants.
Rheumatological Disorders
Patients with rheumatological disorders on methothrexate treatment
Biological: Influenza vaccine
Standard, commercially available, quadrivalent split-vaccine against influenza is given to all study participants.
People living with HIV
People living with HIV on successful antiretroviral treatment
Biological: Influenza vaccine
Standard, commercially available, quadrivalent split-vaccine against influenza is given to all study participants.
Multiple Sclerosis
Patients with multiple sclerosis on treatment with sphingosine-1-phosphate-receptor-agonists
Biological: Influenza vaccine
Standard, commercially available, quadrivalent split-vaccine against influenza is given to all study participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Influenza vaccine elicited humoral immune response
Time Frame: Directly before and 4-6 weeks after Influenza vaccination
The primary endpoint is the baseline variable adjusted fold-change of influenza HAI titers in immunosuppressed patients versus non-immunocompromised controls. The sum of foldchanges of hemagglutinin inhibition assay (HAI) titers 4-6 weeks after influenza vaccination will be adjusted for age, sex and baseline HAI titers by regression analysis as these three baseline variables are reported to affect influenza vaccine responses.
Directly before and 4-6 weeks after Influenza vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Influenza vaccine elicited microneutralisation antibody titers
Time Frame: Directly before and 4-6 weeks after Influenza vaccination
Influenza vaccine elicited microneutralisation titers will be compared between immunocompromised and non-immunocompromised participants.
Directly before and 4-6 weeks after Influenza vaccination
Seroprotection rate after influenza vaccination
Time Frame: Directly before and 4-6 weeks after Influenza vaccination
The investigators will compare the proportion of patients with seroprotective antibody levels (defined as HAI titer ≥1:40) 4-6 weeks after influenza vaccination in healthy controls and immunosuppressed patients. A HAI titer of ≥1:40 is the accepted threshold for seroprotection by the FDA.
Directly before and 4-6 weeks after Influenza vaccination
Vaccine specific T-cell response
Time Frame: Directly before and 4-6 weeks after Influenza vaccination
The investigators will measure influenza specific CD4+ and CD8+ T-cells before- and 4-6 weeks after influenza vaccination. Influenza specific T-cells will be measured by ELISPOT assays. The investigators will report differences in mean increase of influenza specific CD4+ and CD8+ Tcells between immunosuppressed and healthy controls 4-6 weeks after vaccination.
Directly before and 4-6 weeks after Influenza vaccination
Vaccine Reactogenicity
Time Frame: Directly before and 1 week after Influenza vaccination
The investigators will collect participant information on vaccine reactogenicity by questionnaire (attached to the proposal) one week after vaccination. The investigators will report the frequency of moderate and severe reactogenicity-events per patient group and assess correlation with vaccine response by regression analysis.
Directly before and 1 week after Influenza vaccination
Baseline Immune Profile
Time Frame: Directly before Influenza vaccination (same day)

The investigators will assess the impact of following baseline immunological parameters on the vaccine elicited immune response:

  • total serum antibody concentrations (IgM, IgA, IgG)
  • Baseline IFN-Gamma and IL-2 production upon stimulation (QuantiferonMONITOR ®)
  • Pre-vaccination influenza specific CD4+ and CD8+ T-cells
  • Cellular abundance (per/mcl whole-blood and in %) of 37 immune cell populations measured by high-throughput mass cytometry (CyTOF)
  • mRNA expression measured by bulk mRNA sequencing (Transcriptomics)
  • single cell mRNA expression
  • epigenome configuration
Directly before Influenza vaccination (same day)
Change in PBMC gene-expression profiles
Time Frame: Directly before and 1 week after Influenza vaccination
Changes in individual gene expression one week after influenza vaccination measured by bulk mRNA sequencing (Transcriptomics). Reporting of differential gene expression levels and visualisation in heat-maps.
Directly before and 1 week after Influenza vaccination
Baseline Prediction Model for Vaccine Response
Time Frame: Directly before and 4-6 week after Influenza vaccination
Semi-supervised machine learning methods will be applied to develop a model for prediction of influenza vaccine response defined defined by a HAI-Titer fold change ≥ 4. Variables will contain sociodemographic, clinical data and immunologic baseline profiles. Model performance will be evaluated by means of areas under the receiver operating characteristic curve and confusion matrices. The model will be trained, tested and validated by a 70%, 30% and 15% data split respectively.
Directly before and 4-6 week after Influenza vaccination
Gene-Expression Updated Prediction Model for Vaccine Response
Time Frame: Directly before , 1 week and 4-6 week after Influenza vaccination
A Gene-expression updated model will assess the predictive power of vaccine induced change in gene expression by adding early post-vaccination immunologic profile data to the baseline model data.
Directly before , 1 week and 4-6 week after Influenza vaccination
Intestinal microbiome composition of vaccine responders and non-responders
Time Frame: Directly before Influenza vaccination
To assess differently abundant microbiome composition the investigators will collect stool samples for 16s-rDNA sequencing in a subset of patients. The investigators will compare relative abundance of microbial taxa between vaccine-responders and non-responders defined by a HAI-Titer fold change ≥ 4, 4-6 weeks after vaccination.
Directly before Influenza vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Insel Gruppe AG, University Hospital Bern

Investigators

  • Principal Investigator: Cédric Hirzel, PD, MD, University Hospital Bern, Switzerland
  • Principal Investigator: Christine Thurnheer, PD, MD, University Hospital Bern, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 15, 2024

Primary Completion (Actual)

January 31, 2025

Study Completion (Actual)

January 31, 2025

Study Registration Dates

First Submitted

December 12, 2024

First Submitted That Met QC Criteria

December 12, 2024

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Estimated)

March 26, 2025

Last Update Submitted That Met QC Criteria

March 25, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DLF Nr: 5752
  • BASEC-Nr: 2024-01077 (Other Identifier: BASEC (Business Administration System for Ethics Committees) - Switzerland)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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