Safety and Immune Response of Adjuvanted SARS-CoV-2 (COVID-19) Beta Variant RBD Recombinant Protein (DoCo-Pro-RBD-1 + MF59®) and mRNA (MIPSCo-mRNA-RBD-1) Vaccines in Healthy Adults
- Conditions
- SARS-CoV-2
- Interventions
- Biological: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59)Other: Normal SalineBiological: SARS-CoV-2 beta variant RBD mRNA vaccine
- Registration Number
- NCT05272605
- Lead Sponsor
- University of Melbourne
- Brief Summary
This is a study of two experimental SARS-CoV-2 vaccines against the virus called SARS-CoV-2 virus. The first of the experimental vaccines is called DoCo-Pro-RBD-1 + M59® and contains a laboratory made protein which looks the same as a protein in the SARS-CoV-2 virus. As this protein is so similar to a protein in the SARS-CoV-2 virus, it allows the immune system to develop immunity against the real virus by producing specific antibodies against this protein. Antibodies are substances in the blood which could help protect against future infection. The second of the experimental vaccines that will be tested is called MIPSCo-mRNA-RBD-1. This type of vaccine uses messenger ribonucleic acid (mRNA) which is a set of instructions for a cell to make a viral protein called an antigen. Antigens are substances that can trigger the body's defences to produce antibodies that fight against the disease.
This study will test these two experimental COVID-19 vaccines in people who have previously received two doses of ComirnatyTM (Pfizer Australia Pty Ltd) or VaxzevriaTM (AstraZeneca Pty Ltd) and a third booster vaccination with either ComirnatyTM or SpikevaxTM (Moderna). This study is the first time this recombinant protein vaccine and this mRNA vaccine will be given to humans. The purpose of this study is to determine what amount, or dose, of the experimental vaccines is safe and produces the desired immune response and antibody level for future investigations. It will do this by testing 3 different dose levels for each of the two vaccines. Each participant will receive a single vaccine at one of the three dose levels, or a placebo injection. This study is the first time this recombinant protein vaccine and this mRNA vaccine will be given to humans.
- Detailed Description
This is a randomised, double-blind, placebo-controlled, dose-escalation, first-in-human study to assess the safety, reactogenicity and immunogenicity of SARS-CoV-2 beta variant DoCo-Pro-RBD-1 + MF59® and MIPSCo-mRNA-RBD-1 vaccine at three dose levels, administered intramuscularly (IM) as a single booster dose in healthy adults previously vaccinated with two doses of CominartyTM (BNT162b2 \[mRNA\]) or VaxzevriaTM (ChAdOx1-S) COVID-19 and a third booster dose of either ComirnatyTM or SpikevaxTM vaccines. The study will comprise a Dose-Escalation Phase and an Expanded Phase.
The study vaccines, DoCo-Pro-RBD-1 + MF59®, MIPSCo-mRNA-RBD-1 or placebo (normal saline) will be administered IM in the deltoid region of the upper arm.
The study will enroll healthy adults aged 18 to 64 years of age inclusive. Participants in both the Dose-Escalation Phase and Expanded Phase of the study will be stratified by prior primary course COVID-19 vaccination with CominartyTM or VaxzevriaTM.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1)15mcg + MF59 Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) DoCo-Pro-RBD-1 antigen 15mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1 Normal saline (0.9%) Normal Saline Normal saline (0.9%) administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1 SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 50mcg SARS-CoV-2 beta variant RBD mRNA vaccine MIPSCo-mRNA-RBD-1 antigen 50mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1 Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 45mcg + MF59 Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) DoCo-Pro-RBD-1 antigen 45mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1 SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 10mcg SARS-CoV-2 beta variant RBD mRNA vaccine MIPSCo-mRNA-RBD-1 antigen 10mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1 Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 5mcg + MF59 Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) DoCo-Pro-RBD-1 antigen 5mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1 SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 20mcg SARS-CoV-2 beta variant RBD mRNA vaccine MIPSCo-mRNA-RBD-1 antigen 20mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1
- Primary Outcome Measures
Name Time Method Solicited local and systemic reactogenicity AEs post vaccination. Within 7 days after vaccination (Day 1) Frequency, severity, duration and peak intensity
Unsolicited AEs post vaccination. Day 1 to Day 29 (28 days post vaccination). Frequency
Percentage of participants who achieve a boost response post vaccination. 28 days after vaccination Defined as a 4-fold increase in SARS-CoV-2 neutralising or RBD-specific Ab titres from baseline.
Serious adverse events (SAEs), medically attended adverse events (MAAEs) and any adverse events (AEs) leading to study withdrawal at any time during the study. Through to study completion at Day 181. Frequency
SAEs post vaccination. Day 1 to 29 (28 Days post vaccination). Frequency
- Secondary Outcome Measures
Name Time Method MAAEs from Day 1 to 6 months after vaccination. 6 months after vaccination. MeDRA classification, severity score and relatedness.
The ratio of T cell derived type 1 versus type 2 cytokines in participants that mount a T cell response. Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination. For participants that develop a T cell response, the ratio of type 1 cytokine to type 2 cytokines, measured by intracellular cytokine staining and by ELISpot, will be determined for at each timepoint, compared to placebo controls and baseline responses.
The number of participants that develop an antibody response at least 4 times higher than baseline antibody titers. At baseline (Day 1), Day 29 (28 days after vaccination), and 3, and 6 months after vaccination Number of participants that develop an antibody response at least 4 times higher than baseline antibody titers (before injection of the vaccine candidate or placebo), as assessed using in vitro ELISA assays for binding of the SARS-CoV-2 RBD to ACE2, and neutralising antibody assays that measure the ability to block RBD binding to ACE-2 or the ability of virus to infect cells in vitro). The magnitude and durability of those antibody responses over time will also be used to indicate the strength of the response within each participant to each vaccine in each cohort, and in relation to which vaccine the participants had previously received, compared to those participants that received placebo.
Number of participants that mount a T cell response that leads to type-1 cytokines (such as Interferon-gamma) versus type-2 cytokines (such as Interleukin 4, 5 and 13). Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination. For participants that develop a T cell response, two types of T cell response will be assessed, based on whether the activated T cells produce the cytokine Interferon-gamma, indicative of a type 1 cytokine response, or Interleukins 4, 5 and 13, indicative of a type 2 cytokine response. Cytokines will be measured following T cell activation with SARS-CoV-2-derived peptide antigens in vitro, using assays for cytokines will include intracellular cytokine staining as measured by flow cytometry, and elispot, as measured by an elispot reader.
Number of participants that mount a T cell response for SARS-CoV-2 RBD-derived peptide antigens. Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination. Number of participants that develop a T cell response in the short term (Day 8) and in the longer term (Day 29, 3 and 6 months after vaccination) in response to the vaccine candidate compared to their baseline (Day 1) T cell responses. T cell responses will be measured by flow cytometry looking for activated CD4 and CD8 T cells, including the percentage of T cells that respond to peptide antigens derived from the SARS-CoV-2 RBD. The magnitude and durability of those T cell responses over time will also be used to indicate the strength of the response within each participant to each vaccine in each cohort, and in relation to which vaccine the participants had previously received, compared to those participants that received placebo.
Trial Locations
- Locations (2)
Vaccine and Immunisation Research Group, Doherty Institute, University of Melbourne
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital, Victorian Infectious Diseases Service (VIDS)
🇦🇺Melbourne, Victoria, Australia