Evaluation of Full Versus Fractional Dose of COVID-19 Vaccine Given as a Booster for the Prevention of COVID-19 in Adults in Mongolia.

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.

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.

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®)

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.

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®)

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).

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.

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.

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.

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 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.

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).

All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.

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.

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.

Confirmed SARS-CoV-2 infections will be documented throughout the follow-up period, by clinical severity.

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 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.

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).