Influenza Vaccine Elicited Immune Response in Immunocompromised Patients

Completed

• Conditions: Influenza Vaccine; Immunocompromised Patients
• Interventions: Biological: Influenza vaccine

• Registration Number: NCT06738082
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

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.

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 Timeline

• Study Start: 2024-10-15
• Study First Submitted: 2024-12-12
• Study First Submitted QC: 2024-12-12
• Primary Completion: 2025-01-31
• Study Completion: 2025-01-31
• Status Verified: 2025-03
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 147

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CAR-T Cell Recipients	Influenza vaccine	Patients with B-cell malignancies receiving anti-CD19 CAR T-cell therapies
Rheumatological Disorders	Influenza vaccine	Patients with rheumatological disorders on methothrexate treatment
People living with HIV	Influenza vaccine	People living with HIV on successful antiretroviral treatment
Multiple Sclerosis	Influenza vaccine	Patients with multiple sclerosis on treatment with sphingosine-1-phosphate-receptor-agonists
Control Group	Influenza vaccine	Non-immunocompromised controls

Primary Outcome Measures

Name	Time	Method
Influenza vaccine elicited humoral immune response	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.

Secondary Outcome Measures

Name	Time	Method
Baseline Immune Profile	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
Influenza vaccine elicited microneutralisation antibody titers	Directly before and 4-6 weeks after Influenza vaccination	Influenza vaccine elicited microneutralisation titers will be compared between immunocompromised and non-immunocompromised participants.
Seroprotection rate after influenza vaccination	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.
Vaccine specific T-cell response	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.
Vaccine Reactogenicity	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.
Change in PBMC gene-expression profiles	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.
Baseline Prediction Model for Vaccine Response	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.
Gene-Expression Updated Prediction Model for Vaccine Response	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.
Intestinal microbiome composition of vaccine responders and non-responders	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.

Trial Locations

Locations (1)

Universitsy Hospital Bern; 🇨🇭 Bern, Switzerland