Immune Response to Vaccinations in Hematopoietic Stem Cell Transplant Recipients (VaccHemInf)

A Prospective Cohort Study of Efficacy, Safety and Characterization of Immune Response to Vaccinations in Hematopoietic Stem Cell Transplant Recipients

Hematopoietic stem cell transplantation (HSCT) is a cellular therapy aiming at curing some hematological diseases. Upon transplantation, recipients experience a phase of profound immune suppression with loss of protective immunity against most infectious agents. Revaccination of HSCT recipients against vaccine-preventable infections is an important post-transplant intervention for reducing morbi-mortality. The VaccHemInf project aims at assessing the efficacy of recommended vaccines in adult recipients of HSCT, through the antibody titers reference method and a panel of immune functional assays.

Study Overview

• Status: Completed
• Conditions: Vaccination; Hematopoietic Stem Cells
• Intervention / Treatment: Biological: immune biomarkers to evaluate vaccine response in HSCT recipients

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69004
    • Hôpital de la Croix Rousse
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• allogeneic and autologous HSCT recipients
• ≥ 18 year-old
• patients having been informed of the conditions of the study (24-month follow-up) and having signed the informed consent form

• Person with social security insurance

  • Additional inclusion criteria for healthy volunteers enrolled (10 volunteers)in the ancillary study of influenza vaccine response:

• health-care workers recruited from the hospital staff

Exclusion Criteria:

• Patient with innate or acquired immune deficiency (severe combined immunodeficiency, Hepatitis C virus (HCV), HBV, HIV infections at any stage)
• Pregnant or breastfeeding women
• History of previous severe allergic reaction to vaccine components
• Patient with no social security coverage, with restricted liberty or under legal protection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hematopoietic stem cell transplant (HSCT); immune biomarkers to evaluate vaccine response in HSCT recipients	Biological: immune biomarkers to evaluate vaccine response in HSCT recipients; a 38mL-blood sample will be collected before and at 3, 12 and 24 months after complete block vaccination and at 4 weeks after influenza vaccination for the ancillary study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of responders defined by the increase in specific antibody titers at 3 months after full block vaccination including tetanus, diphtheria, Pneumococcus, Haemophilus influenza type B (Hib), and hepatitis B virus (HBV).	ELISA methods will be used to measure serum level concentrations of specific immunoglobulin G (IgG) antibodies to tetanus toxoid, diphtheria toxoid, Hib, pneumococcal capsular polysaccharides and HBV. For pneumococcus, a 4-fold increase in the IgG titer will be considered significant for immunization. For Hib, the values between 0.15-1 μg/mL will be significant for immunization (linearity limit of 9 μg/mL). An IgG titer equal or higher than 0.1 IU/mL for diphtheria and tetanus and higher than 10 mIU/mL for HBV (anti-HBs antibody titer will be considered protective) . An anti-HBs titer higher than 100 IU/mL will be considered to confer long-lasting protection.	at 3 months after block vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of responders defined by the increase in specific antibody titers at 12 months after full block vaccination including tetanus, diphtheria, Pneumococcus, Haemophilus influenza type B (Hib), and hepatitis B virus (HBV).	ELISA methods will be used to measure serum level concentrations of specific IgG antibodies to tetanus toxoid, diphtheria toxoid, Hib, pneumococcal capsular polysaccharides and HBV. For pneumococcus, a 4-fold increase in the IgG titer will be considered significant for immunization. For the Hib, the values between 0.15-1 μg/mL will be significant for immunization (linearity limit of 9 μg/mL). An IgG titer equal or higher than 0.1 IU/mL for diphtheria and tetanus and higher than 10 mIU/mL for HBV (anti-HBs antibody titer) will be considered protective. An anti-HBs titer higher than 100 IU/mL will be considered to confer long-lasting protection	at 12 months after block vaccination
proportion of responders defined by the increase in specific antibody titers at 24 months after full block vaccination including tetanus, diphtheria, Pneumococcus, Haemophilus influenza type B (Hib), and hepatitis B virus (HBV).	ELISA methods will be used to measure serum level concentrations of specific IgG antibodies to tetanus toxoid, diphtheria toxoid, Hib, pneumococcal capsular polysaccharides and HBV. For pneumococcus, a 4-fold increase in the IgG titer will be considered significant for immunization. For the Hib, the values between 0.15-1 μg/mL will be significant for immunization (linearity limit of 9 μg/mL). An IgG titer equal or higher than 0.1 IU/mL for diphtheria and tetanus and higher than 10 mIU/mL for HBV (anti-HBs antibody titer) will be considered protective. An anti-HBs titer higher than 100 IU/mL will be considered to confer long-lasting protection	at 24 months after block vaccination
Correlation between quantification of relevant immune cells of HSCT recipients and vaccine response	the association between blood T- B- and NK cell counts and subtypes of T and B cells (cells /mm3 of whole blood) and vaccine response will be analyzed	at 3, 12 and 24 months after full block vaccination
Correlation between proliferative T-cell response to mitogens and antigens and vaccine response	lymphocyte proliferation in response to ex vivo T cell stimulation (% of proliferating cells among CD3+ T-cells) will be evaluated The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals (RI) derived from an independent set of healthy volunteers (REALISM protocol).	before and at 3 months after full block vaccination
Correlation between innate immune response after ex vivo whole blood stimulation and vaccine response	The production of tumor necrosis factor (TNF) alpha released by blood cells in response to ex vivo stimulation by lipopolysaccharide (in pg/mL) will be measured The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals (RI) derived from an independent set of healthy volunteers (REALISM protocol).	before and at 3 months after full block vaccination
proportion of HSCT recipients with adverse event after each vaccination including local and general reactions	local and general reactions will be monitored for 30 min after each vaccination. Recipients will be given a diary card to record occurrence and severity of specific local reactions at the injection site and specific general reactions for 21 days after each vaccine injection.	21 days after each vaccination
ancillary study of cellular and humoral response to one dose of tetravalent inactivated influenza vaccine (IIV)	Hemagglutination-inhibition assay (HAI) will be used to measure serum level concentrations of specific antibodies to the four influenza strains included in the vaccine. Immunization will be defined by seroprotective antibody titers ≥ 1:40 and/or seroconversion (4-fold rise in antibody titers). T-cell responses elicited by IIV will be measured ex vivo by interferon-Gamma ELISpot assay and expressed as number of spot-forming-cells. T-cell responses will be correlated to influenza antibody production, as measured by hemagglutination-inhibition assay (HAI). Influenza vaccine response in allo-HSCT recipients will be compared to that observed in Healthy Volunteers.	4 weeks after influenza vaccination.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Collaborators: BioMérieux
• Investigators: Principal Investigator: Florence ADER, Pr, Hospices Civils de Lyon

Publications and helpful links

General Publications

• Conrad A, Boccard M, Valour F, Alcazer V, Tovar Sanchez AT, Chidiac C, Laurent F, Vanhems P, Salles G, Brengel-Pesce K, Meunier B, Trouillet-Assant S, Ader F; Lyon HEMINF Study Group. VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients. BMJ Open. 2019 Feb 15;9(2):e026093. doi: 10.1136/bmjopen-2018-026093.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): January 21, 2021
• Study Completion (Actual): January 21, 2023

Study Registration Dates

• First Submitted: July 25, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: vaccination; immune function; Hematopoietic stem cell transplantation; allogeneic hematopoietic stem cell transplantation; vaccines; autologous hematopoietic stem cell transplantation
• Other Study ID Numbers: 69HCL17_0769; 2017-A03230-53 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No