Adaptive Immune Response to COVID-19 Vaccination

Study Overview
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Brief Summary
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AICOVI (Adaptive Immune Response to COVID-19 Vaccination) is a prospective clinical cohort study aiming at studying the kinetics of vaccine-specific antibody production after COVID-19 vaccination in health care workers.

Detailed Description
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AICOVI (Adaptive Immune Response to COVID-19 Vaccination) is a prospective clinical cohort study aiming at elucidating the kinetics of vaccine-specific antibody production after COVID-19 vaccination in health care workers at the Greifswald University hospital. Participants were recruited before their intended vaccination. Participants received the basic immunization with either two i. m. doses of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) with a time interval of 21 days or two i. m. dose of AZD 1222 (Vaxzevria®, Covishield®, ChadOx1 nCoV-19, Oxford University/Astra-Zeneca) with a time interval of 12 weeks (homologous vaccination), or one i. m. dose of AZD 1222 as the first vaccination and one i. m. dose of BNT162b2 or mRNA-1273 (Spikevax®, elasomeran (INN), Moderna) as the second vaccination with a time interval of at least 4 weeks (heterologous vaccination). Approximately 6 months later, participants received a booster vaccination with BNT162b2. Within the study, volunteers donate peripheral blood by venipuncture on each day of vaccination as well as 7 and 14 days after each vaccination. EDTA plasma and peripheral mononuclear cells (PBMCs) are prepared and stored at -20 °C. Volunteers are also asked to complete a standardized questionnaire on each day of blood sampling. Questionnaires collect data about physical characteristics, COVID-19 vaccination, previous SARS-CoV-2 infection as well as current infections, medication, immune relevant diseases and side effects of the vaccination.

Official Title
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Blood Donations From Healthy Probands for the Study of the Adaptive Immune Response to COVID-19 Vaccination (AICOVI)

Conditions
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SARS-CoV-2 Vaccination

Intervention / Treatment
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* Drug: BNT162b2
* Drug: AZD 1222
* Drug: mRNA-1273


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Planned participation in COVID-19 vaccination Completion of the 18th year of life verbal and written consent given Exclusion Criteria: current infectious diseases underweight (BMI<18,5) blood coagulation disorders, anemia or similar diseases known congenital or acquired immunodeficiencies Inclusion criteria for control/validation group of TRP participants: informed written consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BNT/BNT/BNT<br>Subjects receiving two doses of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) as homologous basic immunization and one dose of BNT162b2 as booster vaccination | Drug: BNT162b2<br>* vaccination against COVID-19<br>* Other names: tozinameran;|
| AZD/BNT/BNT<br>Subjects receiving one dose of AZD 1222 (Vaxzevria®, Covishield®, ChadOx1 nCoV-19, Oxford University/Astra-Zeneca) followed by one dose of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) as heterologous basic immunization and one dose of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) as booster vaccination | Drug: BNT162b2<br>* vaccination against COVID-19<br>* Other names: tozinameran;Drug: AZD 1222<br>* vaccination against COVID-19<br>* Other names: ChadOx1 nCoV-19;|
| AZD/AZD/BNT<br>Subjects receiving two doses of AZD 1222 (Vaxzevria®, Covishield®, ChadOx1 nCoV-19, Oxford University/Astra-Zeneca) as homologous basic immunization and one dose of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) as booster vaccination | Drug: BNT162b2<br>* vaccination against COVID-19<br>* Other names: tozinameran;Drug: AZD 1222<br>* vaccination against COVID-19<br>* Other names: ChadOx1 nCoV-19;|
| AZD/MOD/BNT<br>Subject receiving one dose of AZD 1222 (Vaxzevria®, Covishield®, ChadOx1 nCoV-19, Oxford University/Astra-Zeneca) followed by one dose of mRNA-1273 (Spikevax®, elasomeran (INN), Moderna) as heterologous basic immunization and one dose of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) as booster vaccination | Drug: BNT162b2<br>* vaccination against COVID-19<br>* Other names: tozinameran;Drug: AZD 1222<br>* vaccination against COVID-19<br>* Other names: ChadOx1 nCoV-19;Drug: mRNA-1273<br>* vaccination against COVID-19<br>* Other names: elasomeran;|
| AZD/BNT/MOD<br>Subject receiving one dose of AZD 1222 (Vaxzevria®, Covishield®, ChadOx1 nCoV-19, Oxford University/Astra-Zeneca) followed by one dose of BNT162b2 (Comirnaty®, tozinameran (INN), BioNTech/Pfizer) as heterologous basic immunization and one dose of mRNA-1273 (Spikevax®, elasomeran (INN), Moderna) as booster vaccination | Drug: BNT162b2<br>* vaccination against COVID-19<br>* Other names: tozinameran;Drug: AZD 1222<br>* vaccination against COVID-19<br>* Other names: ChadOx1 nCoV-19;Drug: mRNA-1273<br>* vaccination against COVID-19<br>* Other names: elasomeran;|
| Control/validation group<br>Control samples for the validation of the used methods from the pre-SARS-CoV-2 era were transferred from the study Blood Donations from Healthy Blood Donors to Investigate Circannual Variations in Tryptophan Metabolism and Adaptive Immune Response to Bacterial Infectious Agents (in short TRP study). Subjects had not received any SARS-CoV-2 vaccination at that time. Remaining plasma samples were transferred to the AICOVI study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean current anti-SARS-CoV-2 antibody production and cumulative antibody titer on the day of the 1st vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted on the day of the 1st vaccination. | 1 day | 
| mean current anti-SARS-CoV-2 antibody production 7 days after the 1st vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted 7 days after the 1st vaccination. | 7 days after the 1st vaccination | 
| mean current anti-SARS-CoV-2 antibody production 14 days after the 1st vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted 14 days after the 1st vaccination. | 14 days after the 1st vaccination | 
| mean current anti-SARS-CoV-2 antibody production on the day of the 2nd vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted on the day of the 2nd vaccination. | day of the 2nd vaccination | 
| mean current anti-SARS-CoV-2 antibody production 7 days after the 2nd vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted 7 days after the 2nd vaccination. | 7 days after the 2nd vaccination | 
| mean current anti-SARS-CoV-2 antibody production 14 days after the 2nd vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted 14 days after the 2nd vaccination. | 14 days after the 2nd vaccination | 
| mean current anti-SARS-CoV-2 antibody production and cumulative antibody titer on the day of the booster vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted on the day of the booster vaccination. | 1 day | 
| mean current anti-SARS-CoV-2 antibody production 7 days after the booster vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted 7 days after the booster vaccination. | 7 days after the booster vaccination | 
| mean current anti-SARS-CoV-2 antibody production 14 days after the booster vaccination | Serum antibody titers represent a cumulative measure of any preceded or recent immune responses. The current antibody production can be quantified using MENSA (medium enriched for newly synthesized antibodies), an approach that measures antibodies released from recently stimulated circulating antibody-secreting plasmablasts. For this purpose, PBMCs are collected from the subject's whole blood sample, washed to remove serum antibodies, and then cultured for 7 days. Antibodies released ex vivo from the antibody-secreting plasmablasts can now be detected in the culture supernatant. These newly synthesized antibodies are a measure of the instantaneous antibody response. Sampling is conducted 14 days after the booster vaccination. | 14 days after the booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma antibody levels against SARS-CoV-2 | Anti-SARS-CoV-2 antibodies are quantified using ELISA and/or xMAP(R) technology. | On each day of vaccination as well as 7 and 14 days after each vaccination | 
| immune cell phenotyping (B cells, T cells) | flow cytometry-based analyses | On each day of vaccination as well as 7 and 14 days after each vaccination | 
| Characterization of antibody proteomics profile changes after vaccination | The antibody profile in plasma is assessed using mass spectrometry. | On each day of vaccination as well as 7 and 14 days after each vaccination | 
| Characterization of the cytokine profile elicited after vaccination | The cytokine profile elicited after vaccination is assessed using a multiplex immunoassay. | On each day of vaccination as well as 7 and 14 days after each vaccination | 
| Measurement of neutralizating antibodies after vaccination | Neutralizing antibodies are measured by neutralization tests. | On each day of vaccination as well as 7 and 14 days after each vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, vaccination, SARS-CoV-2, COVID-19, immune response, immunokinetics