Humoral and Cellular Immune Response to COVID-19 Vaccines in Immunocompromised and Healthy Individuals (CoVVac)

Humoral and Cellular Immune Response to COVID-19 Vaccines in Immunocompromised and Healthy Individuals - The CoVVac Study

Currently, the efficacy of COVID-19 vaccination in immunodeficient patients is unknown. Here the investigators aim to evaluate the efficacy of COVID-19 vaccines in immunodeficient patients compared to healthy controls. The investigators will assess the humoral and cellular response to COVID-19 vaccination in these subjects in detail. Furthermore, factors associated with good response to vaccination will be identified. The results of this study will help to guide future recommendations on COVID-19 vaccination in this population.

Study Overview

• Status: Completed
• Conditions: Covid19; Immunosuppression
• Intervention / Treatment: Diagnostic test: Blood sample; Diagnostic test: Saliva sample

Detailed Description

The total duration of the study is 38 months, starting in March 2021 with a recruiting period until 31. December 2021 and termination of all scheduled visits until 31 May 2024. Individuals having consented and fulfilling the inclusion and exclusion criteria are included in the trial. A baseline visit will take place up to 60 days before the planned date of vaccination according to the Austrian vaccination plan. Scheduled vaccination with any COVID-19 vaccine approved in Austria will allow recruitment. If appropriate pre-vaccine samples from study participants exist in the biobank of the Medical University of Graz, patients may also be included in the study after vaccination starting with visit 3. In this case the biomaterial available at the biobank will be used for the analyses planned on visit 1. The investigators will not influence the date of vaccination or the type of the vaccine used. After first vaccination a telephone visit (visit 2) will assess adverse events and schedule visit 3 at the appropriate time after the second vaccination. At visit 3 the patient's vaccination certificate will be checked to verify correct vaccination and document the type of vaccine received. Further visits (5-6) will be performed for up to two years after the second vaccination. This follow-up period will allow an assessment of the duration of the immune response. The data recorded directly on the Case Report Form (CRF) are considered to be source data. COVID-19 vaccination, COVID-19 infection, Vaccination history, Pregnancy test, Adverse Events, BMI (Body Mass Index), and Laboratory Specimen Collection are recorded directly on the CRF and therefore are considered to be source data. Data will be merged in an electronic database (RDA Research, Documentation & Analysis; Medical University of Graz, version 07.03.2019). Case Report Forms (CRFs) will be inspected in respect of their accuracy and completeness and compared to original data by the monitor.

• Study Type: Observational
• Enrollment (Actual): 373

Contacts and Locations

• Study Contact: Name: Martin Stradner, Prof.; Phone Number: 81794 +43316385; Email: Martin.stradner@medunigraz.at

Study Locations

• Austria
  • Graz, Austria
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Immunodeficient participants and immunocompetent participants (i.e., healthy participants)

Description

Inclusion Criteria:

1. Noninfectious immunocompetent participants (i.e., healthy participants) as determined by medical history and clinical judgement.

   or

2. Patients with primary immunodeficiencies or
3. Patients with B-cell depleting therapy due to autoimmune disease or

4. Patients with benign and malignant hematological diseases receiving specific Treatments with known immunosuppressive effects including cytotoxic agents, systemic corticosteroids, monoclonal antibodies and targeted therapies.

   or

5. Patients with active hematological diseases and secondary immunoglobulin deficiency (e.g. chronic lymphatic leukemia, MM) currently not receiving specific treatment.

   or

6. Patients >3 months but <12 months after autologous HSCT (hematopoietic stem cell transplantation).

   or

7. Patients >3 months but <12 months after allogeneic HSCT. or

8. Recipients of HSCT >12 months after allogeneic HSCT but under immunosuppressive therapy.

   or

9. Patients with chronic GvHD (graft-versus-host disease) and persistent immunodeficiency.

Exclusion Criteria:

Healthy participants

1. Presence of diseases or therapies that are likely to interfere with the immune response to vaccination.
2. Presence of a disease requiring change in therapy during 4 weeks before enrollment.
3. Any contraindications to the vaccine planned to receive as listed in the product characteristics.
4. Lack of willingness to undergo serial blood draws and attend follow-up appointments.
5. Women who are pregnant or breastfeeding.
6. Previous vaccination with any coronavirus vaccine.
7. Persons who are not willing to sign the informed consents (biobank informed consent and study specific informed consent).

Immunodeficient participants

1. Patients with hematological diseases within three months from B-cell-depleting immunotherapy (rituximab, ofatumumab, obinutuzumab, blinatumomab, CAR-T cells (Chimeric Antigen Receptor).
2. Patients with hematological malignancies in remission and >12 months after end of specific therapy.
3. Patients within three months from HSCT.
4. Any contraindications to the vaccine planned to receive as listed in the product characteristics.
5. Lack of willingness to undergo serial blood draws and attend follow-up appointments.
6. Women who are pregnant or breastfeeding.
7. Previous vaccination with any coronavirus vaccine (exception: if serum prior to vaccination is available from the biobank).
8. Patients who are not willing to sign the informed consents (biobank informed consent and study specific informed consent).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Immunocompromised individuals; Patients with primary or secondary immunodeficiency planning on vaccination against SARS CoV-2 according to the Austrian vaccination plan.	Diagnostic test: Blood sample; Serology, immune status, T cell immunity, and T cell aging.; Diagnostic test: Saliva sample; Antibody tests
Healthy individuals; Healthy people planning on vaccination against SARS CoV-2 according to the Austrian vaccination plan.	Diagnostic test: Blood sample; Serology, immune status, T cell immunity, and T cell aging.; Diagnostic test: Saliva sample; Antibody tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The levels of anti-SARS-CoV-2 spike protein humoral immune response.	The levels of anti-SARS-CoV-2 (severe acute respiratory syndrome-Covid Virus) spike protein humoral immune response measured by SARS-CoV-2 antigen-binding Ig assay comparing immunocompromised patients to healthy controls.	At day 21-28 after the second vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion	Change of Seroconversion measured by SARS-CoV-2 antigen-binding Ig assay 6, 12 and 24 months after vaccination.	6, 12 and 24 months after vaccination.
Concentrations of recombinant S protein-binding IgG (immunoglobulin G)	Change of Concentrations of recombinant S protein-binding IgG after second vaccination in comparison to response after first vaccination.	At day 21-28 as well as 12 and 24 months after the second vaccination.
Concentrations of secretory and serum IgA in comparison to IgG and IgM (immunoglobulin M)	Change of Concentrations of secretory and serum IgA in comparison to IgG and IgM after second vaccination in immunocompromised, in recovered individuals and in healthy controls.	At day 21-28 as well as 12 and 24 months after the second vaccination.
IFNγ production of T cells	Change of IFNγ (Interferone gamma) production of T cells after SARS-CoV-2 antigen exposure, measured by FACS (fluorescence-activated cell sorter) and ELISpot.	At day 21-28 as well as 12 and 24 months after the second vaccination.
Cross-reactive antibodies predicting the response to COVID-19 vaccinations	Identification of parameters predicting the response to COVID-19 vaccinations: prior CoV infection (cross-reactive antibodies). Evaluation of the influence of previous infections caused by endemic CoV (proven through cross-reactive antibodies) on the vaccine response in immunocompromised individuals and in COVID-19 recovered individuals compared to controls.	At day 21-28 as well as 12 and 24 months after the second vaccination.
Quantitative immunoglobulins predicting the response to COVID-19 vaccinations	Identification of parameters predicting the response to COVID-19 vaccinations: quantitative immunoglobulins.	At day 21-28 as well as 12 and 24 months after the second vaccination.
B cell subsets predicting the response to COVID-19 vaccinations	Identification of parameters predicting the response to COVID-19 vaccinations: B cell subsets.	At day 21-28 as well as 12 and 24 months after the second vaccination.
T cell subsets predicting the response to COVID-19 vaccinations	Identification of parameters predicting the response to COVID-19 vaccinations: T cell subsets.	At day 21-28 as well as 12 and 24 months after the second vaccination.
T cell aging predicting the response to COVID-19 vaccinations	Identification of parameters predicting the response to COVID-19 vaccinations: T cell aging (TCR diversity, telomere length, TREC levels).	60-0 days before first vaccination.
Occurence of neutralizing antibodies by means of SARS-CoV-2 neutralizing assays.	Neutralizing capacity of antibodies in respect of different SARSCoV-2 variants.	At day 21-28 as well as 12 and 24 months after the second vaccination.
Correlation of diet and body fat with seroconversion	Correlation of diet and body fat with seroconversion after second vaccination.	At day 21-28 and 12 months after the second vaccination.

Collaborators and Investigators

• Sponsor: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 19, 2021
• Primary Completion (ACTUAL): January 20, 2023
• Study Completion (ACTUAL): January 20, 2023

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (ACTUAL): April 26, 2021

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Vaccination
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CoVVac

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