Efficacy and Safety of Heterologous and Homologous COVID-19 Vaccination

Comparative Analysis of Neutralizing Antibody Response Among Heterologous ChAdOx1-nCov-19/mRNA-1273 Vaccination and Homologous ChAdOx1-nCov-19 or Homologous mRNA-1273 Vaccination

The investigators conduct a prospective analysis to compare homologous and heterologous adenovirus vector ChAdOx1-nCov-19 (Astra-Zeneca) or SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine inoculation. Healthy volunteers will be enrolled and divided into five groups. The first group is the subjects who received ChAdOx1- nCov-19 vaccine with 8 weeks apart; the second group is the SARS-CoV-2 messenger RNA-1273 vaccine after the first dose of ChAdOx1-nCov-19 vaccination with 8 weeks apart; the third group is the first dose of ChAdOx1-nCov-19 vaccine and the SARS-CoV-2 messenger RNA-1273 vaccine with 4 weeks apart; the fourth group is the SARS-CoV-2 messenger RNA-1273 vaccination with 4 weeks apart; the fifth group is the first dose of ChAdOx1-nCov-19 vaccine and the SARS-CoV-2 messenger RNA-1273 vaccine with 12 weeks apart. There will be 100 volunteers in each group. Antibody test on the day before and the 14th, 28th day and 12th week after the second dose of vaccination, including 100 subjects in each group for SARS-CoV-2 ELISA antibody titer and 50 people in each group for SARS-CoV-2 neutralizing antibody titer. Adverse reactions at the first day, the 14th day, the 28th day, and the 12th week. The research team follow up each volunteer at the 6th month.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Volunteers
• Intervention / Treatment: Biological: ChAdOx1-nCov-19 (Astra-Zeneca); Biological: SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine

Detailed Description

The investigators would like to conduct a prospective analysis to compare the same adenovirus vector ChAdOx1-nCov-19 (Astra-Zeneca) or SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine inoculation and mixed inoculation of ChAdOx1-nCov-19 and messenger RNA-1273 vaccine. Healthy volunteers (including medical personnel) will be enrolled and divided into five groups according to their wishes. The five groups are: the first group is the subjects who received ChAdOx1- nCov-19 vaccine with 8 weeks apart; the second group is the SARS-CoV-2 messenger RNA-1273 vaccine after the first dose of ChAdOx1-nCov-19 vaccination with 8 weeks apart; the third group is the first dose of ChAdOx1-nCov-19 vaccine and the SARS-CoV-2 messenger RNA-1273 vaccine with 4 weeks apart; the fourth group is the SARS-CoV-2 messenger RNA-1273 vaccination with 4 weeks apart; the fifth group is the first dose of ChAdOx1-nCov-19 vaccine and the SARS-CoV-2 messenger RNA-1273 vaccine with 12 weeks apart. There will be 100 volunteers in each group, and blood will be drawn for antibody test on the day before and the 14th, 28th day and 12th week after the second dose of vaccination, including 100 subjects in each group for SARS-CoV-2 ELISA antibody titer and 50 people in each group for SARS-CoV-2 neutralizing antibody titer. This study analyzo the titers of SARS-CoV-2 antibodies, and records adverse reactions at each visits including the first day, the 14th day, the 28th day, and the 12th week (including those within 7 days after the inoculation). Adverse reactions and whether there is development of COVID-19 within 6 months will be recorded. The research team will also follow up by phone in the 6th month to ask whether there is vaccine associated adverse events or SARS-CoV-2 infection. The results will provide information for vaccine policy in Taiwan.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • X
    • Taipei City, X, Taiwan, 10002
      • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females aged ≥20 to <65 years old and have received adenovirus vector vaccine ChAdOx1-nCov-19 (Astra-Zeneca) or SARS-CoV-2 messenger RNA-1273 once within three months at least four weeks apart.
2. The subject must sign the subject's inform consent, or the subject's legal representative must understand and agree, then sign inform consent according to procedure above.
3. Healthy or existing medical condition is stable, and within 3 months before being included in the trial, he or she has not been hospitalized due to illness, and his or her condition is expected to remain stable during the trial period.

Exclusion Criteria:

1. Are currently pregnant or breastfeeding or plan to become pregnant within 30 days after the second dose of the trial vaccine.
2. Currently receiving or receiving other vaccines, including Streptococcus pneumoniae vaccine.
3. Have used any blood products or intravenous immunoglobulin within 12 weeks before entering the test. Receive concurrent immunosuppressive or immunomodulatory therapy (including steroid prednisone, targeted drugs such as infliximab, adalimumab, etanercept) within 12 weeks.
4. Immunosuppressive diseases or immune insufficiency states, including hematological malignancies, parenchymal organs, bone marrow transplant history or asplenia, autoimmune diseases (systemic lupus, rheumatoid arthritis, scleroderma, polyarthritis, autoimmune thyroiditis, etc.) and human immunodeficiency virus infection.
5. Bleeding disease and assessed as a contraindication to prohibit the use of intramuscular injection or blood draw.
6. Other condition, such as physical examination or instability according to the trial investigator's judgment, or participation in this trial may adversely affect the safety of subjects, fail to comply with trial regulations, or interfere with trial evaluation indicators.
7. The subject is known to have been infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Heterologous ChAdOx1-nCov-19 vaccination - 8 weeks apart; Astra-Zeneca vaccine 0.5 mL/dose	Biological: ChAdOx1-nCov-19 (Astra-Zeneca); vaccine inoculation and mixed inoculation
Active Comparator: mRNA-1273 Vaccination and Heterologous ChAdOx1-nCov-19 vaccination- 8 weeks apart; Moderna COVID-19 Vaccine 0.5 mL/dose and Astra-Zeneca vaccine 0.5 mL/dose	Biological: ChAdOx1-nCov-19 (Astra-Zeneca); vaccine inoculation and mixed inoculation; Biological: SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine; vaccine inoculation and mixed inoculation
Active Comparator: Heterologous ChAdOx1-nCov-19 vaccination and the mRNA-1273 Vaccination- 4 weeks apart; Moderna COVID-19 Vaccine 0.5 mL/dose and Astra-Zeneca vaccine 0.5 mL/dose	Biological: ChAdOx1-nCov-19 (Astra-Zeneca); vaccine inoculation and mixed inoculation; Biological: SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine; vaccine inoculation and mixed inoculation
Active Comparator: The mRNA-1273 Vaccination- 4 weeks apart; Moderna COVID-19 Vaccine 0.5 mL/dose	Biological: SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine; vaccine inoculation and mixed inoculation
Active Comparator: Heterologous ChAdOx1-nCov-19 vaccination and the mRNA-1273 Vaccination-12 weeks apart; Moderna COVID-19 Vaccine 0.5 mL/dose and Astra-Zeneca vaccine 0.5 mL/dose	Biological: ChAdOx1-nCov-19 (Astra-Zeneca); vaccine inoculation and mixed inoculation; Biological: SARS-CoV-2 messenger RNA-1273 (Moderna) vaccine; vaccine inoculation and mixed inoculation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Samples for by using enzyme-linkes immuno sorbent assay (ELISA) at 14th,28th,12 th week and 6 months after the second dose.	Neutralizing antibody response among heterologous and heterologous COVID-19 vaccination and homologous	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Sample for spike-specific CD4+ T cells		6 months
Blood Sample for production of interferon(IFN)-γ	(pg/mL)	6 months
Blood Sample for tumor necrosis factor (TNF)-α	(pg/mL)	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events and severe adverse events at 14th,28th,12 th week and 6months after the second dose.	6 months
severe adverse events	Adverse events and severe adverse events at 14th,28th,12 th week and 6months after the second dose.	6 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Taoyuan General Hospital, Ministry of Health and Welfare,Taoyuan,Taiwan

Publications and helpful links

General Publications

• Sheng WH, Chang SY, Lin PH, Hsieh MJ, Chang HH, Cheng CY, Yang HC, Pan CF, Ieong SM, Chao TL, Chen JP, Cheng SH, Chang SC. Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination. J Formos Med Assoc. 2022 Apr;121(4):766-777. doi: 10.1016/j.jfma.2022.02.020. Epub 2022 Mar 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): April 27, 2022
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 16, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; adverse events; humoral immunity; Coronavirus disease 2019 (COVID-19); adenovirus-vector ChAdOx1 vaccination; messenger RNA (mRNA-1273 )vaccination
• Other Study ID Numbers: 202106039MINA

Drug and device information, study documents

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