COVID-19
Conditions
Keywords
Booster dose, Pfizer, fractional and standard doses, COVID-19 vaccination, mRNA vaccine
Brief summary
This clinical trial is a single-blind, randomised study to determine the reactogenicity and immunogenicity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccine (Pfizer-BioNTech) as booster dose in adults, who have previously received either Sinopharm (BBIBP-CorV®), AstraZeneca (ChAdOx1-S, or Vaxzevria®) or Sputnik V (Gam-COVID-Vac®) as their primary doses 6 to 9 months earlier. Both standard and fractional doses will be tested. Participants are healthy adults aged 18 years or older, with no upper age limit. Procedures will be implemented to ensure participants of all ages (aged 18 and above) are included and that there is an even age distribution (\<50 and ≥50 years) in each group. There will be a total of 6 groups (Sinopharm-standard dose Pfizer, Sinopharm-fractional dose Pfizer, AstraZeneca-standard dose Pfizer, AstraZeneca-fractional dose Pfizer, Sputnik - standard dose Pfizer, Sputnik - fractional dose Pfizer), with 200 participants per group for Sinopharm and 100 for AstraZeneca and Sputnik.
Detailed description
As per brief summary
Interventions
BIOLOGICALTozinameran - Standard Dose
Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dose - 30 µg in 0.3 ml. Liquid for injection. Single dose.
BIOLOGICALTozinameran - Fractional Dose
Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dose - 15 µg in 0.15 ml. Liquid for injection. Single dose.
Sponsors
Murdoch Childrens Research Institute
Coalition for Epidemic Preparedness Innovations
The Peter Doherty Institute for Infection and Immunity
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 28 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product allocation. Laboratory staff will remain blinded to the investigational product allocation during the immunology testing.
Intervention model description
Study participants who have received two doses of either Sinopharm, AstraZeneca or Sputnik vaccine as their primary vaccine will be randomised into one of two groups. The two groups consist of a standard or fractional dose of Pfizer vaccine.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Have completed two doses of Sinopharm, AstraZeneca or Sputnik vaccines with the recommended schedule 6 months prior to the date of enrolment 2. Willing and able to give written informed consent 3. Aged 18 years or above 4. Willing to complete the follow-up requirements of the study
Exclusion criteria
1. Received 3 doses of COVID-19 vaccine 2. Received 2 doses of COVID-19 less than 6 months prior to the start of the trial 3. Currently on immunosuppressive medication or anti-cancer chemotherapy 4. HIV infection 5. Congenital immune deficiency syndrome 6. Has received immunoglobulin or other blood products in the 3 months prior to vaccination 7. Study staff and their relatives 8. Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroresponse | 28-days post booster vaccination | Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. The primary endpoint is the seroresponse rate at the Day-28 visit. The seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of \<200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of \>200 BAU/ml, or a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection. |
| Solicited Grade 3 or 4 Local or Systemic Reaction | 7 days post booster vaccination | Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report grade 3 or 4 reactions by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration, swelling, fever, nausea, vomiting, headache, fatigue/malaise, myalgia, arthralgia, diarrhea, enlarged lymph nodes will be collected from the participants 7 days post-vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroresponse by Priming Vaccine Strata | 28-days post booster vaccination | Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. The primary endpoint is the seroresponse rate at the Day-28 visit. The seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of \<200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of \>200 BAU/ml, or a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection. Priming strata (previously COVID vaccination): AstraZeneca (ChAdOx1-S, or Vaxzevria®); Sinopharm (BBIBP-CorV®); Sputnik V (Gam-COVID-Vac®) |
| SARS-CoV-2 Specific IgG Antibodies at Day-28 | 28-days post booster vaccination | Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. |
| SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 28-days post booster vaccination | Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. Priming strata (previously COVID vaccination): AstraZeneca (ChAdOx1-S, or Vaxzevria®); Sinopharm (BBIBP-CorV®); Sputnik V (Gam-COVID-Vac®) |
| SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre-booster), 28 Days, 6 Months, 12 Months, 18 Months, and 24 Months Post-booster Vaccination. | Baseline (pre booster), 28 days, 6 months, 12 months, 18 months, and 24 months post-booster vaccination. | Serum samples collected at baseline (pre booster), 28 days, 6 months, 12 months, 18 months, and 24 months post booster vaccination from the study arms will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units (BAU)/mL and presented as geometric mean concentration (GMC) and 95% confidence intervals (CI). |
| SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre-booster), 28 Days, 6 Months, 12 Months, 18 Months, and 24 Months Post-booster Vaccination Measured by Surrogate Virus Neutralisation Test (sVNT). | Baseline (pre-booster), 28 days, 6 months, 12 months, 18 months, and 24 months post-booster vaccination. | Serum samples collected at baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific neutralising antibodies using the GenScript® cPass surrogate virus neutralization test (sVNT) for both wild-type and Omicron variant. Neutralising antibody response will be reported as percentage (%) inhibition of receptor binding domain-angiotensin-converting enzyme 2 (RBD-ACE2) binding relative to a positive control. |
| SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days-, 6- and 12-months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay | Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination | A subset of samples (20%) from all four timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre. |
| Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Baseline (pre booster), 28 days, 6-, 12 -, 18-, and 24-months post booster vaccination | IFN-γ concentrations (IU/mL) as a measure of cellular immunity will be assessed in a subset of participants. IFN-γ production will be stimulated using QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) and quantified by ELISA. Results are summarised as geometric mean concentrations (GMCs) with 95% confidence intervals. |
| Number of IFNγ Producing Cells/Million PBMCs | Baseline (pre-booster), 28 days, 6 and 12 months post booster vaccination | Applicable to the subset participants with additional blood collection. IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset of the participants (40%) from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFNγ producing cells/million and presented using means and 95% CI. |
| Frequency of Cytokine-expressing T Cells | Baseline (pre-booster), 28 days, 6 and 12 months post-booster vaccination | Frequency of wild-type SARS-CoV-2 spike-specific cytokine-expressing T cells will be assessed in a subset of participants (\~40%) using intracellular cytokine staining (ICS) by flow cytometry on PBMC samples. Results are reported as the frequency (%) of cytokine-expressing CD4 and CD8 memory T cells, summarised as geometric mean concentrations (GMCs) with 95% confidence intervals. |
| Cellular Immunity: Multiplex Cytokine Assays - Reported as Cytokine Concentrations in pg/ml and Presented as GMC and 95% CI | Baseline (pre booster), 28 days-, 6 and 12 months post booster vaccination | Wild-type SARS-CoV-2 spike-specific cytokine concentrations following PBMC stimulation will be assessed in a predefined subset of participants (approximately 40%) using multiplex cytokine assays. Cytokine concentrations will be reported in pg/mL and summarised as geometric mean concentrations (GMCs) with 95% confidence intervals. IFN-γ ELISpot, intracellular cytokine staining (flow cytometry), and multiplex cytokine assays will be performed on isolated peripheral blood mononuclear cells (PBMCs). |
| Incidence of Unsolicited Adverse Events (AE) | 28 days-post booster vaccination | All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE. |
| Incidence of Medically Attended Adverse Events | 3 months post booster vaccination | All participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as number of participants who report unsolicited AE. |
| Incidence of Serious Adverse Events (SAE) | 24 months post-booster | SAE will be collected throughout the follow-up period of 24 months post booster vaccination. Data will be presented as a proportion of participants who report unsolicited SAE. |
| Incidence of PCR Confirmed COVID-19 Infection | Up to 24 months post booster vaccination | Confirmed SARS-CoV-2 infections will be documented throughout the follow-up period, by clinical severity. |
Countries
Mongolia
Contacts
PRINCIPAL_INVESTIGATORTsetsegsaikhan Batmunkh, MD
Ministry of Health, Mongolia
PRINCIPAL_INVESTIGATORKim Mulholland, MD/Prof
Murdoch Childrens Research Institute
Participant flow
Pre-assignment details
There are two study arms (i.e. groups to which participants were randomised), as per "Arms and Interventions" in Protocol Section, corresponding to the primary analysis comparing a full dose to a fractional dose. Stratified randomisation was performed to ensure balanced randomisation according to the primary vaccine received (prior to this study) and age for secondary subgroup analyses. The Participant Flow was edited to reflect the randomisation of participants into two arms.
Participants by arm
| Arm | Count |
|---|---|
| AstraZeneca (ChAdOx1-S, or Vaxzevria®) - Standard Pfizer-BioNTech Booster Group Previously received two doses of AstraZeneca as primary COVID-19 vaccine
Tozinameran - Standard Dose: Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 30 µg in 0.3 ml. Liquid for injection. Single dose. | 65 |
| AstraZeneca (ChAdOx1-S, or Vaxzevria®) - Fractional Pfizer-BioNTech Booster Group Previously received two doses of AstraZeneca as primary COVID-19 vaccine
.
Tozinameran - Fractional Dose: Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 15 µg in 0.15 ml. Liquid for injection. Single dose. | 65 |
| Sinopharm (BBIBP-CorV®)- Standard Pfizer-BioNTech Booster Group Previously received two doses of Sinopharm as primary COVID-19 vaccine
Tozinameran - Standard Dose: Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 30 µg in 0.3 ml. Liquid for injection. Single dose. | 201 |
| Sinopharm (BBIBP-CorV®)- Fractional Pfizer-BioNTech Booster Group Previously received two doses of Sinopharm as primary COVID-19 vaccine
Tozinameran - Fractional Dose: Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 15 µg in 0.15 ml. Liquid for injection. Single dose. | 200 |
| Sputnik V (Gam-COVID-Vac®)- Standard Pfizer-BioNTech Booster Group Previously received two doses of Sputnik as primary COVID-19 vaccine
Tozinameran - Standard Dose: Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 30 µg in 0.3 ml. Liquid for injection. Single dose. | 34 |
| Sputnik V (Gam-COVID-Vac®)- Fractional Pfizer-BioNTech Booster Group Previously received two doses of Sputnik as primary COVID-19 vaccine
Tozinameran - Fractional Dose: Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 15 µg in 0.15 ml. Liquid for injection. Single dose. | 36 |
| Total | 601 |
Baseline characteristics
| Characteristic | AstraZeneca (ChAdOx1-S, or Vaxzevria®) - Standard Pfizer-BioNTech Booster Group | AstraZeneca (ChAdOx1-S, or Vaxzevria®) - Fractional Pfizer-BioNTech Booster Group | Sinopharm (BBIBP-CorV®)- Standard Pfizer-BioNTech Booster Group | Sinopharm (BBIBP-CorV®)- Fractional Pfizer-BioNTech Booster Group | Sputnik V (Gam-COVID-Vac®)- Standard Pfizer-BioNTech Booster Group | Sputnik V (Gam-COVID-Vac®)- Fractional Pfizer-BioNTech Booster Group | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 9 Participants | 14 Participants | 4 Participants | 1 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 65 Participants | 189 Participants | 186 Participants | 30 Participants | 35 Participants | 570 Participants |
| Age, Continuous | 34.5 years | 40.2 years | 47.8 years | 48.8 years | 43.1 years | 41.3 years | 44 years |
| BMI | 26.3 kg/m2 | 25.4 kg/m2 | 24.6 kg/m2 | 24.8 kg/m2 | 25.3 kg/m2 | 25.8 kg/m2 | 25.2 kg/m2 |
| Race and Ethnicity Not Collected | — | — | — | — | — | — | 0 Participants |
| Region of Enrollment Mongolia | 65 participants | 65 participants | 201 participants | 200 participants | 34 participants | 36 participants | 601 participants |
| Sex: Female, Male Female | 33 Participants | 32 Participants | 115 Participants | 114 Participants | 19 Participants | 14 Participants | 327 Participants |
| Sex: Female, Male Male | 32 Participants | 33 Participants | 86 Participants | 86 Participants | 15 Participants | 22 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 65 | 0 / 201 | 0 / 200 | 0 / 34 | 0 / 36 |
| other Total, other adverse events | 5 / 65 | 7 / 65 | 10 / 201 | 7 / 200 | 5 / 34 | 5 / 36 |
| serious Total, serious adverse events | 0 / 65 | 2 / 65 | 2 / 201 | 0 / 200 | 1 / 34 | 0 / 36 |
Outcome results
Primary
Seroresponse
Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. The primary endpoint is the seroresponse rate at the Day-28 visit. The seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of \<200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of \>200 BAU/ml, or a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection.
Time frame: 28-days post booster vaccination
Population: The analysis of immunogenicity endpoints included all participants with outcome data.~There are two study arms, as per Arms and Interventions in Protocol Section, corresponding to the primary analysis comparing a full dose to a fractional dose. Stratified randomisation was performed to ensure balanced randomisation according to the primary vaccine received (prior to this study) and age for secondary subgroup analyses. The primary outcome is unstratified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard | Seroresponse | 253 Participants |
| Fractional | Seroresponse | 250 Participants |
Comparison: Non-inferiority margin of -10% (absolute difference) and a one-sided significance level of 5%.95% CI: [-7.7, 2]Regression, Logistic
Primary
Solicited Grade 3 or 4 Local or Systemic Reaction
Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report grade 3 or 4 reactions by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration, swelling, fever, nausea, vomiting, headache, fatigue/malaise, myalgia, arthralgia, diarrhea, enlarged lymph nodes will be collected from the participants 7 days post-vaccination.
Time frame: 7 days post booster vaccination
Population: The reactogenicity and safety analysis populations included all randomised participants who received a study vaccine, according to the vaccine received.~There are two study arms, as per Arms and Interventions in Protocol Section. Stratified randomisation was performed to ensure balanced randomisation according to the primary vaccine received (prior to this study) and age for secondary subgroup analyses. The primary outcome is unstratified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard | Solicited Grade 3 or 4 Local or Systemic Reaction | 6 Participants |
| Fractional | Solicited Grade 3 or 4 Local or Systemic Reaction | 4 Participants |
Secondary
Cellular Immunity: Multiplex Cytokine Assays - Reported as Cytokine Concentrations in pg/ml and Presented as GMC and 95% CI
Cytokine concentrations following PBMCs stimulation will be assessed on a subset of participants (40%) using multiplex cytokine assays.Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.IFN-γ Elispot, intracellular cytokine assays (flow cytometry) and multiplex cytokine assays will be performed on isolated PBMCs.
Time frame: Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination
Secondary
Frequency of Cytokine-expressing T Cells
Frequency of cytokine-expressing T cells will be assessed on a subset of participants (40%) using flow cytometry (intracellular staining) on PBMCs samples. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.
Time frame: Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months)
Secondary
Incidence of Medically Attended Adverse Events
All participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.
Time frame: 3 months post booster vaccination
Secondary
Incidence of PCR Confirmed COVID-19 Infection
Confirmed COVID-19 infections will be documented throughout the follow-up period, by clinical severity.
Time frame: Up to 12 months post booster vaccination
Secondary
Incidence of Serious Adverse Events (SAE)
SAE will be collected throughout the follow-up period of 12 months post booster vaccination. Data will be presented as a proportion of participants who report unsolicited SAE.
Time frame: 12 months post booster vaccination
Secondary
Incidence of Unsolicited Adverse Events (AE)
All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.
Time frame: 28 days-post booster vaccination
Population: The reactogenicity and safety analysis populations included all randomised participants who received a study vaccine, according to the vaccine received
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard | Incidence of Unsolicited Adverse Events (AE) | 5 Participants |
| Fractional | Incidence of Unsolicited Adverse Events (AE) | 9 Participants |
| Sinopharm (BBIBP-CorV®)- Standard Pfizer-BioNTech Booster Group | Incidence of Unsolicited Adverse Events (AE) | 12 Participants |
| Sinopharm (BBIBP-CorV®)- Fractional Pfizer-BioNTech Booster Group | Incidence of Unsolicited Adverse Events (AE) | 7 Participants |
| Sputnik V (Gam-COVID-Vac®)- Standard Pfizer-BioNTech Booster Group | Incidence of Unsolicited Adverse Events (AE) | 5 Participants |
| Sputnik V (Gam-COVID-Vac®)- Fractional Pfizer-BioNTech Booster Group | Incidence of Unsolicited Adverse Events (AE) | 5 Participants |
Secondary
Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL
Applicable to the subset participants with additional blood collection. Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in peripheral blood mononuclear cells (PBMCs) and then IFN-γ production will be measured using ELISA (enzyme-linked immunosorbent assay). Data will be presented as GMC and 95% CI.
Time frame: Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination
Secondary
Number of IFNγ Producing Cells/Million PBMCs
Applicable to the subset participants with additional blood collection. IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset of the participants (40%) from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFNγ producing cells/million and presented using means and 95% CI.
Time frame: Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination
Secondary
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), 28- Days, 6- and 12-months Post Booster Vaccination.
Serum samples collected at baseline (pre booster), 28 days, 6- and 12-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG CMIA. Data will be reported as binding antibody units (BAU)/mL and presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).
Time frame: Baseline (pre booster), 28 days, 6- and 12-months post booster vaccination
Secondary
SARS-CoV-2 Specific IgG Antibodies at Day-28
Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA.
Time frame: 28-days post booster vaccination
Population: The analysis of immunogenicity endpoints included all participants with outcome data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Standard | SARS-CoV-2 Specific IgG Antibodies at Day-28 | 4946 BAU/ml |
| Fractional | SARS-CoV-2 Specific IgG Antibodies at Day-28 | 4619 BAU/ml |
p-value: 0.22895% CI: [0.86, 1.04]Regression, Linear
Secondary
SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata
Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. Priming strata (previously COVID vaccination): AstraZeneca (ChAdOx1-S, or Vaxzevria®); Sinopharm (BBIBP-CorV®); Sputnik V (Gam-COVID-Vac®)
Time frame: 28-days post booster vaccination
Population: The analysis of immunogenicity endpoints included all participants with outcome data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Standard | SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 4394 BAU/ml |
| Fractional | SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 4167 BAU/ml |
| Sinopharm (BBIBP-CorV®)- Standard Pfizer-BioNTech Booster Group | SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 5109 BAU/ml |
| Sinopharm (BBIBP-CorV®)- Fractional Pfizer-BioNTech Booster Group | SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 4970 BAU/ml |
| Sputnik V (Gam-COVID-Vac®)- Standard Pfizer-BioNTech Booster Group | SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 5160 BAU/ml |
| Sputnik V (Gam-COVID-Vac®)- Fractional Pfizer-BioNTech Booster Group | SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata | 3662 BAU/ml |
p-value: 0.53795% CI: [0.77, 1.15]Regression, Linear
p-value: 0.92295% CI: [0.89, 1.11]Regression, Linear
p-value: 0.01495% CI: [0.54, 0.93]Regression, Linear
Secondary
SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days-, 6- and 12-months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay
A subset of samples (20%) from all four timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre.
Time frame: Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination
Secondary
SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days-, 6- and 12-months Post Booster Vaccination Measured by Surrogate Virus Neutralization Test (sVNT).
Serum samples collected at baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific neutralising antibodies using the GenScript® cPass surrogate virus neutralization test (sVNT) for both wild-type and Omicron variant. Neutralising antibody response will be reported as percentage (%) inhibition of receptor binding domain-angiotensin-converting enzyme 2 (RBD-ACE2) binding relative to a positive control.
Time frame: Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination
Secondary
Seroresponse by Priming Vaccine Strata
Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG ELISA. The primary endpoint is the seroresponse rate at the Day-28 visit. The seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of \<200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of \>200 BAU/ml, or a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection. Priming strata (previously COVID vaccination): AstraZeneca (ChAdOx1-S, or Vaxzevria®); Sinopharm (BBIBP-CorV®); Sputnik V (Gam-COVID-Vac®)
Time frame: 28-days post booster vaccination
Population: The analysis of immunogenicity endpoints included all participants with outcome data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard | Seroresponse by Priming Vaccine Strata | 55 Participants |
| Fractional | Seroresponse by Priming Vaccine Strata | 52 Participants |
| Sinopharm (BBIBP-CorV®)- Standard Pfizer-BioNTech Booster Group | Seroresponse by Priming Vaccine Strata | 170 Participants |
| Sinopharm (BBIBP-CorV®)- Fractional Pfizer-BioNTech Booster Group | Seroresponse by Priming Vaccine Strata | 169 Participants |
| Sputnik V (Gam-COVID-Vac®)- Standard Pfizer-BioNTech Booster Group | Seroresponse by Priming Vaccine Strata | 28 Participants |
| Sputnik V (Gam-COVID-Vac®)- Fractional Pfizer-BioNTech Booster Group | Seroresponse by Priming Vaccine Strata | 29 Participants |
95% CI: [-16.1, 11.3]Regression, Logistic
95% CI: [-9.5, 3.2]Regression, Logistic
95% CI: [-17.1, 16.1]Regression, Logistic