Adaptive Immune Response to COVID-19 Vaccination (AICOVI)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: SARS-CoV-2 Vaccination
• Intervention / Treatment: Drug: BNT162b2; Drug: AZD 1222; Drug: mRNA-1273

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Germany
  • MV
    • Greifswald, MV, Germany, 17475
      • University Medicine Greifswald

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Employees at the University Medicine Greifswald, Germany, who plan to be vaccinated against COVID-19

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BNT/BNT/BNT; 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; vaccination against COVID-19; Other Names: Comirnaty®; tozinameran
AZD/BNT/BNT; 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; vaccination against COVID-19; Other Names: Comirnaty®; tozinameran; Drug: AZD 1222; vaccination against COVID-19; Other Names: Vaxzevria®; Covishield®; ChadOx1 nCoV-19
AZD/AZD/BNT; 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; vaccination against COVID-19; Other Names: Comirnaty®; tozinameran; Drug: AZD 1222; vaccination against COVID-19; Other Names: Vaxzevria®; Covishield®; ChadOx1 nCoV-19
AZD/MOD/BNT; 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; vaccination against COVID-19; Other Names: Comirnaty®; tozinameran; Drug: AZD 1222; vaccination against COVID-19; Other Names: Vaxzevria®; Covishield®; ChadOx1 nCoV-19; Drug: mRNA-1273; vaccination against COVID-19; Other Names: Spikevax®; elasomeran
AZD/BNT/MOD; 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; vaccination against COVID-19; Other Names: Comirnaty®; tozinameran; Drug: AZD 1222; vaccination against COVID-19; Other Names: Vaxzevria®; Covishield®; ChadOx1 nCoV-19; Drug: mRNA-1273; vaccination against COVID-19; Other Names: Spikevax®; elasomeran
Control/validation group; 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?

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

Collaborators and Investigators

• Sponsor: University Medicine Greifswald
• Investigators: Study Chair: Barbara M. Bröker, Prof. Dr., University Medicine Greifswald, Dept. of Immunology

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2021
• Primary Completion (Actual): December 13, 2021
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; vaccine; COVID-19; vaccination; immune response; immunokinetics
• 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: BB 001/21f

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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