Reactogenicity, Immunogenicity and Inflammatory Response by New COVID-19 Vaccine Platforms

Different Significance of Reactogenicity in Immunogenicity and Inflammatory Response by New COVID-19 Vaccine Platforms: BNT162b2 mRNA Versus ChAdOx1 nCoV19 Vaccine

Analysis of humoral antibody and cytokine kinetics after vaccination with either BNT162b2 or ChAdOx1 nCoV-19 vaccine and factors influencing the vaccine immunogenicity

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Vaccine Adverse Reaction; Vaccine Immune Response; COVID-19 Vaccination
• Intervention / Treatment: Biological: either BNT162b2 or ChAdOx1 vaccine

Detailed Description

There is a different aspect of reactogenicity between BNT162b2 and ChAdOx1 nCoV-19 vaccine. Both new platform vaccines were concerned if they would elicit more significant local or systemic reactogenicity compared to the conventional vaccines. Previous studies had reported that immune cells such as mast cells and macrophages are activated just after vaccination, and release proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. The post-vaccination kinetics of inflammatory cytokines would be variable by each vaccine platform, and might be associated with reactogenicity. It is an interesting issue to be investigated whether the reactogenicity following newly developed BNT162b2 and ChAdOx1 would be associated with immunogenicity and inflammatory response or not. To better clarify these uncertainties, we evaluated the change of antibody response between BNT162b2 and ChAdOx1 over three months post-vaccination, in relation to the kinetics of inflammatory cytokines and reactogenicity.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Joon Young Song, MD; Phone Number: +82226263052; Email: infection@korea.ac.kr
• Study Contact Backup: Name: Jung Yeon Heo, MD; Phone Number: +82312197818; Email: jyeon78@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • KangNam Sacred Heart Hospital
    • Contact: Yu Bin Seo
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Joon Young Song; Email: infection@korea.ac.kr
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of
      • Recruiting
      • Ajou University School of Medicine
      • Contact: Jung Yeon Heo; Email: jyeon78@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 59 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy young adults between the ages of 19 and 55 years who were willing to receive either BNT162b2 or ChAdOx1 were enrolled in the study and provided written informed consent

Description

Inclusion Criteria:

• Volunteers who provide the informed consent after either BNT162b2 or ChAdOx1 vaccination
• healthy adults without underlying medical condition

Exclusion Criteria:

• Volunteers who had ever infected with SARS-CoV2 were excluded.

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
ChAdOx1 vaccine group; AstraZeneca vaccine (chimpanzee adenovirus-vectored vaccine, 0.5 mL [5 × 1010 viral particles] per dose)	Biological: either BNT162b2 or ChAdOx1 vaccine; Either BNT162b2 or ChAdOx1 was assigned to each participant by the Korean governmental policy, not allowing personal choice. Sixty participants were vaccinated with two doses of the ChAdOx1 (AstraZeneca) at 12-week intervals, and the remaining sixty were immunized with the BNT162b2 (Pfizer-BioNTech) vaccine at 3-week interval.
BNT162b2 vaccine group; Pfizer-BioNTech vaccine (mRNA vaccine; 0.3 mL [30 μg] per dose)	Biological: either BNT162b2 or ChAdOx1 vaccine; Either BNT162b2 or ChAdOx1 was assigned to each participant by the Korean governmental policy, not allowing personal choice. Sixty participants were vaccinated with two doses of the ChAdOx1 (AstraZeneca) at 12-week intervals, and the remaining sixty were immunized with the BNT162b2 (Pfizer-BioNTech) vaccine at 3-week interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunoglobulin G (IgG) anti-S antibodies	measured using the Elecsys® Anti-SARS-CoV-2 S assay (Roche, Rotkreuz, Switzerland)	At 3 weeks after the first-dose vaccination (T1)
Immunoglobulin G (IgG) anti-S antibodies	measured using the Elecsys® Anti-SARS-CoV-2 S assay (Roche, Rotkreuz, Switzerland)	At 3 weeks after the second-dose vaccination (T2)
Neutralizing antibodies	Reduction in plaque count of 50% (PRNT50) was calculated for the median neutralizing titer (ND50) using the Spearman-Karber formula	At 3 weeks after the first-dose vaccination (T1)
Neutralizing antibodies	Reduction in plaque count of 50% (PRNT50) was calculated for the median neutralizing titer (ND50) using the Spearman-Karber formula	At 3 weeks after the second-dose vaccination (T2)
IL-6, TNF-α, and IL-1ß	measured by flexible customized bead-based multiplex panels for Luminex assays (Human Premixed Multi-Analyte Kit, R&D Systems Inc., Minneapolis, MN, USA).	At 3 days after the first dose
IL-6, TNF-α, and IL-1ß	measured by flexible customized bead-based multiplex panels for Luminex assays (Human Premixed Multi-Analyte Kit, R&D Systems Inc., Minneapolis, MN, USA).	At 3 days after the second-dose
reactogenicity after vaccination	Local erythema/swelling was regarded as positive sign if larger than 2.5 cm in diameter. Systemic adverse events were graded as follows: grade 0, no systemic adverse event; grade 1, any adverse event that did not interfere with activity; grade 2, any adverse event that interfered with daily activity. Fever was classified as grade 1 (from 37.5℃ to 38.4℃) and grade 2 (>38.5℃). Systemic adverse events were classified into two ways: (i) the highest level of severity of any adverse event reported by the participants and (ii) with or without specific adverse event.	Until post-vaccination day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between humoral immune response and reactogenicity after vaccination	The correlation between humoral immune response and reactogenicity after vaccination	The correlation between reactogenicity after the first dose and immunogenicity at T1 (3 weeks after dose 1 prior to dose 2) and T2 (3 weeks after dose 2);the correlation between reactogenicity after vaccine dose 2 and immunogenicity at T2
The correlation between cytokine response and reactogenicity after vaccination	The correlation between cytokine response and reactogenicity after vaccination	At 3 days after each dose
Long-term immunogenicity: Immunoglobulin G (IgG) anti-S antibodies	measured using the Elecsys® Anti-SARS-CoV-2 S assay (Roche, Rotkreuz, Switzerland)	At 3 months after the second vaccination (T3)

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Collaborators: Ajou University School of Medicine; Korean Center for Disease Control and Prevention; Hallym University Kangnam Sacred Heart Hospital
• Investigators: Study Chair: Joon Young Song, MD, Korea University Guro Hospital; Principal Investigator: Jung Yeon Heo, MD, Ajou University School of Medicine; Principal Investigator: Yu Bin Seo, MD, Hallym University Kangnam Sacred Heart Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): May 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 6, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: reactogenicity; immunogenicity
• Additional Relevant MeSH Terms: Pathologic Processes; 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; Inflammation
• Other Study ID Numbers: 2021GR0099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: We will make a decision after discussion with the staff of other hospitals. We will share data on adverse events and immunogenicity.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes