The Immune Response of Heterologous Boost Third Dose of mRNA and Protein COVID-19 Vaccine

NCT05132855 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 202101767A3
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

Brief Summary

The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) specific antibody and neutralizing antibody level induced by adenovirus vector vaccines were lower than mRNA vaccines. Vaccine efficacy of ChAdOx1 nCoV-19 was lower than BNT162b2 and mRNA 1273 in clinical trials. The emergence of highly transmissible and mutant variants of SARS-COV-2 has raised the concern of COVID-19 vaccine effectiveness. The complete vaccination rate is still low in Taiwan. Strict border control measures are imposed by Central Epidemic Command Center. However, the measure of quarantine for flight crew is considered one of the breach of COVID-19 infection control. Despite most of the flight crew has fully vaccinated, several episodes of breakthrough infection occurred among flight crew resulting in domestic infection recently. Low neutralizing antibody was found in a proportion of fully vaccinated flight crew and healthcare workers. A 3rd booster COVID-19 dose is considered for flight crew and healthcare workers. This study is to determine the safety, reactogenicity, and immunogenicity of heterologous 3rd booster of mRNA and protein COVID-19 vaccines.

Conditions

COVID-19; Breakthrough Infection

Keywords

COVID-19; Breakthrough infection; Heterologous vaccine booster; mRNA vaccine; Protein subunit vaccine

Outcome Measures

Primary Outcomes (4)

• The immune response after heterologous boost third dose of COVID-19 vaccines after homologous prime-boost AZD1222 vaccination

  Immunogenicity studies include SARS-CoV-2 anti-spike IgG, the 50% neutralizing antibody titer (NT50) and IFN - secreting T cells specific to whole spike protein.

  Day 28 after third dose boost

• The immune response after heterologous boost third dose of COVID-19 vaccines after homologous prime-boost AZD1222 vaccination

  Immunogenicity studies include SARS-CoV-2 anti-spike IgG, the 50% neutralizing antibody titer (NT50), IFN - secreting T cells specific to whole spike protein, and Memory T cell epitopes and memory B cell epitopes by flow cytometry.

  Day 180 after third dose boost

• The immune response after heterologous boost fourth dose of COVID-19 vaccines after homologous prime-boost AZD1222 vaccination

  Immunogenicity studies include SARS-CoV-2 anti-spike IgG, the 50% neutralizing antibody titer (NT50), IFN - secreting T cells specific to whole spike protein, and Memory T cell epitopes and memory B cell epitopes by flow cytometry.

  Day 28 after second booster vaccination.

• The immune response of breakthrough infection after heterologous boost third dose of COVID-19 vaccines after homologous prime-boost AZD1222 vaccination

  Immunogenicity studies include SARS-CoV-2 anti-spike IgG, the 50% neutralizing antibody titer (NT50), IFN - secreting T cells specific to whole spike protein, and Memory T cell epitopes and memory B cell epitopes by flow cytometry.

  Day 28 after breakthrough infection (after receiving third doses of any COVID-19 vaccine)

Secondary Outcomes (1)

• The safety of heterologous boost third dose of COVID-19 vaccines

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Study Arms (4)

Booster group 1 (BNT162b2 30ug)

EXPERIMENTAL

The participants in this group will receive BNT162b2 30ug as the booster dose.

Biological: BNT162b2

Booster group 2 (mRNA-1273 50ug)

EXPERIMENTAL

The participants in this group will receive mRNA-1273 50ug as the booster dose.

Biological: mRNA-1273

Booster group 3 (mRNA-1273 100ug)

EXPERIMENTAL

The participants in this group will receive mRNA-1273 100ug as the booster dose.

Biological: mRNA-1273

Booster group 4 (MVC-COV1901 15ug)

EXPERIMENTAL

The participants in this group will receive MCV COVID-19 vaccine 15ug as the booster dose.

Biological: MVC-COV1901

Interventions

BNT162b2 BIOLOGICAL

BNT162b2 is an mRNA vaccine to prevent COVID-19 infection and is approved by the emergency use of authorization (EUA) by the Taiwan FDA.

Booster group 1 (BNT162b2 30ug)

mRNA-1273 BIOLOGICAL

mRNA-1273 is an mRNA vaccine to prevent COVID-19 infection and is approved by the emergency use of authorization (EUA) by the Taiwan FDA.

Booster group 2 (mRNA-1273 50ug); Booster group 3 (mRNA-1273 100ug)

MVC-COV1901 BIOLOGICAL

MCV COVID-19 vaccine is a protein subunit vaccine containing S2P S-protein which passes the EUA by Taiwan FDA.

Booster group 4 (MVC-COV1901 15ug)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing to give written informed consent for participation in the trial.
• Participants should receive 2 doses of the AZD1222. Evidence of this will be gathered from medical history and/or medical records including the COVID-19 vaccine registration yellow card.

You may not qualify if:

• The participant may not enter the trial if ANY of the following apply:
• Fever or evidence of upper respiratory tract infections
• Confirmed COVID-19 cases (PCR-confirmed infection or detectable anti-nucleocapsid protein IgG)
• History of anaphylaxis, severe allergic disease, or reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the listed ingredients of any study vaccine).
• Malignancy requiring receipt of immunosuppressive chemotherapy or radiotherapy for treatment of solid organ cancer/hematological malignancy within the 6 months prior to enrollment.
• Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venipuncture.
• Has received vaccines other than COVID-19 vaccine within one month
• Pregnancy or willingness/intention to become pregnant within 3 months post booster vaccine
• Aged \< 20 years or unable to sign the informed consent
• Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study, or impair interpretation of the study data or insufficient level of language to undertake all study requirements in the opinion of the Investigators.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead
• Medigen Vaccine Biologics Corp.: collaborator

Study Sites (1)

Chang Gung Memorial Hospital

Taoyuan, 333, Taiwan

Location

Related Publications (4)

• Hillus D, Schwarz T, Tober-Lau P, Vanshylla K, Hastor H, Thibeault C, Jentzsch S, Helbig ET, Lippert LJ, Tscheak P, Schmidt ML, Riege J, Solarek A, von Kalle C, Dang-Heine C, Gruell H, Kopankiewicz P, Suttorp N, Drosten C, Bias H, Seybold J; EICOV/COVIM Study Group; Klein F, Kurth F, Corman VM, Sander LE. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. Lancet Respir Med. 2021 Nov;9(11):1255-1265. doi: 10.1016/S2213-2600(21)00357-X. Epub 2021 Aug 13.

  PMID: 34391547 BACKGROUND

• Liu X, Shaw RH, Stuart ASV, Greenland M, Aley PK, Andrews NJ, Cameron JC, Charlton S, Clutterbuck EA, Collins AM, Dinesh T, England A, Faust SN, Ferreira DM, Finn A, Green CA, Hallis B, Heath PT, Hill H, Lambe T, Lazarus R, Libri V, Long F, Mujadidi YF, Plested EL, Provstgaard-Morys S, Ramasamy MN, Ramsay M, Read RC, Robinson H, Singh N, Turner DPJ, Turner PJ, Walker LL, White R, Nguyen-Van-Tam JS, Snape MD; Com-COV Study Group. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet. 2021 Sep 4;398(10303):856-869. doi: 10.1016/S0140-6736(21)01694-9. Epub 2021 Aug 6.

  PMID: 34370971 BACKGROUND

• Normark J, Vikstrom L, Gwon YD, Persson IL, Edin A, Bjorsell T, Dernstedt A, Christ W, Tevell S, Evander M, Klingstrom J, Ahlm C, Forsell M. Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination. N Engl J Med. 2021 Sep 9;385(11):1049-1051. doi: 10.1056/NEJMc2110716. Epub 2021 Jul 14. No abstract available.

  PMID: 34260850 BACKGROUND

• Chuang CH, Huang CG, Huang CT, Chen YC, Kung YA, Chen CJ, Chuang TC, Liu CC, Huang PW, Yang SL, Gu PW, Shih SR, Chiu CH. Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial. J Clin Virol. 2022 Dec;157:105328. doi: 10.1016/j.jcv.2022.105328. Epub 2022 Nov 12.

  PMID: 36399969 DERIVED

MeSH Terms

Conditions

COVID-19; Breakthrough Infections

Interventions

BNT162 Vaccine; 2019-nCoV Vaccine mRNA-1273; MVC-COV1901 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Officials

• Cheng-Hsun Chiu, MD, PhD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2021
• First Posted: November 24, 2021
• Study Start: November 30, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: July 25, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)