Influenza Vaccine Elicited Immune Response in Immunocompromised Patients

NCT06738082 | Completed

• 2 other identifiers: DLF Nr: 5752BASEC-Nr: 2024-01077
• Study Type: observational
• Target: 147
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza Vaccine; Immunocompromised Patients

Keywords

influenza; immunocompromised; vaccination; vaccine; CAR-T

Outcome Measures

Primary Outcomes (1)

• Influenza vaccine elicited humoral immune response

  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 Outcomes (9)

• Influenza vaccine elicited microneutralisation antibody titers

  Directly before and 4-6 weeks after Influenza vaccination

• Seroprotection rate after influenza vaccination

  Directly before and 4-6 weeks after Influenza vaccination

• Vaccine specific T-cell response

  Directly before and 4-6 weeks after Influenza vaccination

• Vaccine Reactogenicity

  Directly before and 1 week after Influenza vaccination

• Baseline Immune Profile

  Directly before Influenza vaccination (same day)

Study Arms (5)

Control Group

Non-immunocompromised controls

Biological: Influenza vaccine

CAR-T Cell Recipients

Patients with B-cell malignancies receiving anti-CD19 CAR T-cell therapies

Biological: Influenza vaccine

Rheumatological Disorders

Patients with rheumatological disorders on methothrexate treatment

Biological: Influenza vaccine

People living with HIV

People living with HIV on successful antiretroviral treatment

Biological: Influenza vaccine

Multiple Sclerosis

Patients with multiple sclerosis on treatment with sphingosine-1-phosphate-receptor-agonists

Biological: Influenza vaccine

Interventions

Influenza vaccine BIOLOGICAL

Standard, commercially available, quadrivalent split-vaccine against influenza is given to all study participants.

CAR-T Cell Recipients; Control Group; Multiple Sclerosis; People living with HIV; Rheumatological Disorders

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Universitsy Hospital Bern

Bern, 3010, Switzerland

Location

Related Publications (18)

• Manuel O, Humar A, Berutto C, Ely L, Giulieri S, Lien D, Meylan PR, Weinkauf J, Pascual M, Nador R, Aubert JD, Kumar D. Low-dose intradermal versus intramuscular trivalent inactivated seasonal influenza vaccine in lung transplant recipients. J Heart Lung Transplant. 2011 Jun;30(6):679-84. doi: 10.1016/j.healun.2011.01.705. Epub 2011 Mar 5.

  PMID: 21377898 BACKGROUND

• van de Witte S, Nauta J, Montomoli E, Weckx J. A Phase III randomised trial of the immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in adult and elderly subjects, assessing both anti-haemagglutinin and virus neutralisation antibody responses. Vaccine. 2018 Sep 25;36(40):6030-6038. doi: 10.1016/j.vaccine.2018.04.043. Epub 2018 Apr 27.

  PMID: 29709447 BACKGROUND

• Pepin S, Donazzolo Y, Jambrecina A, Salamand C, Saville M. Safety and immunogenicity of a quadrivalent inactivated influenza vaccine in adults. Vaccine. 2013 Nov 12;31(47):5572-8. doi: 10.1016/j.vaccine.2013.08.069. Epub 2013 Sep 7.

  PMID: 24016810 BACKGROUND

• Lindemann M, Witzke O, Lutkes P, Fiedler M, Kreuzfelder E, Philipp T, Roggendorf M, Grosse-Wilde H. ELISpot assay as a sensitive tool to detect cellular immunity following influenza vaccination in kidney transplant recipients. Clin Immunol. 2006 Sep;120(3):342-8. doi: 10.1016/j.clim.2006.03.002. Epub 2006 Apr 21.

  PMID: 16631409 BACKGROUND

• Riese P, Trittel S, Akmatov MK, May M, Prokein J, Illig T, Schindler C, Sawitzki B, Elfaki Y, Floess S, Huehn J, Blazejewski AJ, Strowig T, Hernandez-Vargas EA, Geffers R, Zhang B, Li Y, Pessler F, Guzman CA. Distinct immunological and molecular signatures underpinning influenza vaccine responsiveness in the elderly. Nat Commun. 2022 Nov 12;13(1):6894. doi: 10.1038/s41467-022-34487-z.

  PMID: 36371426 BACKGROUND

• Ravichandran S, Erra-Diaz F, Karakaslar OE, Marches R, Kenyon-Pesce L, Rossi R, Chaussabel D, Nehar-Belaid D, LaFon DC, Pascual V, Palucka K, Paust S, Nahm MH, Kuchel GA, Banchereau J, Ucar D. Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults. Nat Immunol. 2024 Feb;25(2):316-329. doi: 10.1038/s41590-023-01717-5. Epub 2024 Jan 5.

  PMID: 38182669 BACKGROUND

• Hirzel C, Chruscinski A, Ferreira VH, L'Huillier AG, Natori Y, Han SH, Cordero E, Humar A, Kumar D; Influenza in Transplant Study Group. Natural influenza infection produces a greater diversity of humoral responses than vaccination in immunosuppressed transplant recipients. Am J Transplant. 2021 Aug;21(8):2709-2718. doi: 10.1111/ajt.16503. Epub 2021 Feb 18.

  PMID: 33484237 BACKGROUND

• Cheuvart B, Spiessens B, van Heesbeen R, Hung D, Andrade C, Korejwo-Peyramond J, Tavares-Da-Silva F. Harmonizing the collection of solicited adverse events in prophylactic vaccine clinical trials. Expert Rev Vaccines. 2023 Jan-Dec;22(1):849-859. doi: 10.1080/14760584.2023.2262571. Epub 2023 Oct 9.

  PMID: 37750613 BACKGROUND

• Reber A, Katz J. Immunological assessment of influenza vaccines and immune correlates of protection. Expert Rev Vaccines. 2013 May;12(5):519-36. doi: 10.1586/erv.13.35.

  PMID: 23659300 BACKGROUND

• Nakaya HI, Hagan T, Duraisingham SS, Lee EK, Kwissa M, Rouphael N, Frasca D, Gersten M, Mehta AK, Gaujoux R, Li GM, Gupta S, Ahmed R, Mulligan MJ, Shen-Orr S, Blomberg BB, Subramaniam S, Pulendran B. Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures. Immunity. 2015 Dec 15;43(6):1186-98. doi: 10.1016/j.immuni.2015.11.012.

  PMID: 26682988 BACKGROUND

• Caldera F, Mercer M, Samson SI, Pitt JM, Hayney MS. Influenza vaccination in immunocompromised populations: Strategies to improve immunogenicity. Vaccine. 2021 Mar 15;39 Suppl 1:A15-A23. doi: 10.1016/j.vaccine.2020.11.037. Epub 2021 Jan 7.

  PMID: 33422377 BACKGROUND

• Huang D, Liu AYN, Leung KS, Tang NLS. Direct Measurement of B Lymphocyte Gene Expression Biomarkers in Peripheral Blood Transcriptomics Enables Early Prediction of Vaccine Seroconversion. Genes (Basel). 2021 Jun 25;12(7):971. doi: 10.3390/genes12070971.

  PMID: 34202032 BACKGROUND

• Tsang JS, Dobano C, VanDamme P, Moncunill G, Marchant A, Othman RB, Sadarangani M, Koff WC, Kollmann TR. Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome? Trends Immunol. 2020 Jun;41(6):457-465. doi: 10.1016/j.it.2020.04.001. Epub 2020 Apr 8.

  PMID: 32340868 BACKGROUND

• Hagan T, Gerritsen B, Tomalin LE, Fourati S, Mule MP, Chawla DG, Rychkov D, Henrich E, Miller HER, Diray-Arce J, Dunn P, Lee A; Human Immunology Project Consortium (HIPC); Levy O, Gottardo R, Sarwal MM, Tsang JS, Suarez-Farinas M, Sekaly RP, Kleinstein SH, Pulendran B. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses. Nat Immunol. 2022 Dec;23(12):1788-1798. doi: 10.1038/s41590-022-01328-6. Epub 2022 Oct 31.

  PMID: 36316475 BACKGROUND

• Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, Hillert J, Langer-Gould A, Lycke J, Nilsson P, Salzer J, Svenningsson A, Vrethem M, Olsson T, Piehl F, Frisell T. Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurol. 2020 Feb 1;77(2):184-191. doi: 10.1001/jamaneurol.2019.3365.

  PMID: 31589278 BACKGROUND

• Stewart AG, Henden AS. Infectious complications of CAR T-cell therapy: a clinical update. Ther Adv Infect Dis. 2021 Aug 24;8:20499361211036773. doi: 10.1177/20499361211036773. eCollection 2021 Jan-Dec.

  PMID: 34457269 BACKGROUND

• Furer V, Rondaan C, Heijstek M, van Assen S, Bijl M, Agmon-Levin N, Breedveld FC, D'Amelio R, Dougados M, Kapetanovic MC, van Laar JM, Ladefoged de Thurah A, Landewe R, Molto A, Muller-Ladner U, Schreiber K, Smolar L, Walker J, Warnatz K, Wulffraat NM, Elkayam O. Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD. RMD Open. 2019 Sep 19;5(2):e001041. doi: 10.1136/rmdopen-2019-001041. eCollection 2019.

  PMID: 31673420 BACKGROUND

• GBD 2017 HIV collaborators. Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Lancet HIV. 2019 Dec;6(12):e831-e859. doi: 10.1016/S2352-3018(19)30196-1. Epub 2019 Aug 19.

  PMID: 31439534 BACKGROUND

Related Links

• Word Health Organization. Correlates of vaccine-induced protection: methods and implications. World Health Organization, 2013:
• Swiss Federal Office of Public Health (FOPH)

Biospecimen

Retention: SAMPLES WITH DNA

Serum, EDTA Blood, PBMCs

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Christine Thurnheer, PD, MD

  University Hospital Bern, Switzerland

  PRINCIPAL INVESTIGATOR

• Cédric Hirzel, PD, MD

  University Hospital Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 17, 2024
• Study Start: October 15, 2024
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)