Clinical trial NCT04858607: Humoral and Cellular Immune Response to COVID-19 Vaccines in Immunocompromised and Healthy Individuals
Official title: Humoral and Cellular Immune Response to COVID-19 Vaccines in Immunocompromised and Healthy Individuals - The CoVVac Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Immunosuppression
Keywords: Vaccination
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2021-04-26
Enrollment: 373
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Immunodeficient participants and immunocompetent participants (i.e., healthy participants)

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: The levels of anti-SARS-CoV-2 spike protein humoral immune response.
timeFrame: At day 21-28 after the second vaccination
Secondary outcomes:
measure: Seroconversion
timeFrame: 6, 12 and 24 months after vaccination.
measure: Concentrations of recombinant S protein-binding IgG (immunoglobulin G)
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: Concentrations of secretory and serum IgA in comparison to IgG and IgM (immunoglobulin M)
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: IFNγ production of T cells
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: Cross-reactive antibodies predicting the response to COVID-19 vaccinations
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: Quantitative immunoglobulins predicting the response to COVID-19 vaccinations
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: B cell subsets predicting the response to COVID-19 vaccinations
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: T cell subsets predicting the response to COVID-19 vaccinations
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: T cell aging predicting the response to COVID-19 vaccinations
timeFrame: 60-0 days before first vaccination.
measure: Occurence of neutralizing antibodies by means of SARS-CoV-2 neutralizing assays.
timeFrame: At day 21-28 as well as 12 and 24 months after the second vaccination.
measure: Correlation of diet and body fat with seroconversion
timeFrame: At day 21-28 and 12 months after the second vaccination.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
Study officials:
affiliation: Medical University of Graz
name: Martin Stradner, Prof.
role: PRINCIPAL_INVESTIGATOR
References: