Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial
Study Details
Study Description
Brief Summary
Since the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen in late 2019, millions of people around the world have fallen ill and died from coronavirus disease 2019 (COVID-19), with variant-fueled case spikes causing repeated cycles of morbidity and mortality. The rapid development and emergency use authorization of vaccines against SARS-CoV-2 presents an enormous opportunity to protect populations, but bottlenecks in production have led to demand for vaccines that far outpaces supply. This project will investigate the immunogenicity of fractional doses of SARS-CoV-2 vaccines given a minimum of six months following an initial two-dose schedule or following natural immunity via documented infection. The consortium of research partners from the Sabin Vaccine Institute, Aga Khan University, Fundação Oswaldo Cruz (Fiocruz), and Stanford University will recruit volunteers to receive a full or fractional booster dose of BNT162b2, AZD1222 or Sinovac following receipt of their primary vaccination series or PCR-confirmed natural infection in Pakistan. The research team will follow participants for six months from boosting, with blood draws at baseline, 28 days, 3 months and 6 months, and measure sero-response rate (SRR) by anti-Spike immunoglobulin G (IgG) binding enzyme-linked immunosorbent assay (ELISA) with the ultimate aim of identifying whether fractional doses provide a similar immune response compared to full doses of vaccine.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Priming Group 1: Sinovac Prime, AZD1222 ½ dose
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Active Comparator: Priming Group 1: Sinovac Prime, AZD1222 full dose
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Experimental: Priming Group 1: Sinovac Prime, BNT162b2 1/3 dose
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Experimental: Priming Group 1: Sinovac Prime, BNT162b2 1/2 dose
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Active Comparator: Priming Group 1: Sinovac Prime, BNT162b2 full dose
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Active Comparator: Priming Group 1: Sinovac Prime, Sinovac full dose
|
Biological: Sinovac
Sinovac inactivated COVID-19 vaccine:
● Full dose (0.5 ml)
|
Experimental: Priming Group 2: AZD1222 Prime, AZD1222 ½ dose
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Active Comparator: Priming Group 2: AZD1222 Prime, AZD1222 full dose
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Experimental: Priming Group 2: AZD1222 Prime, BNT162b2 1/3 dose
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Experimental: Priming Group 2: AZD1222 Prime, BNT162b2 1/2 dose
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Active Comparator: Priming Group 2: AZD1222 Prime, BNT162b2 full dose
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Experimental: Priming Group 3-B: BNT162b2 Prime, AZD1222 ½ dose (Brazil only)
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Active Comparator: Priming Group 3-B: BNT162b2 Prime, AZD1222 full dose (Brazil only)
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Experimental: Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/3 dose (Brazil only)
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Experimental: Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/2 dose (Brazil only)
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Active Comparator: Priming Group 3-B: BNT162b2 Prime, BNT162b2 full dose (Brazil only)
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Experimental: Priming Group 3-P: Natural Infection Prime, AZD1222 ½ dose (Pakistan only)
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Active Comparator: Priming Group 3-P: Natural Infection Prime, AZD1222 full dose (Pakistan only)
|
Biological: AZD1222
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:
Full dose (0.5 ml)
Half dose (0.25 ml)
|
Experimental: Priming Group 3-P: Natural Infection Prime, BNT162b2 1/3 dose (Pakistan only)
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Experimental: Priming Group 3-P: Natural Infection Prime, BNT162b2 1/2 dose (Pakistan only)
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Active Comparator: Priming Group 3-P: Natural Infection Prime, BNT162b2 full dose (Pakistan only)
|
Biological: BNT162b2
Pfizer/BioNTech BNT162b2 mRNA vaccine:
Full dose (30 micrograms)
Half dose (15 micrograms)
One-third dose (10 micrograms)
|
Outcome Measures
Primary Outcome Measures
- Sero-response rate by Spike IgG binding ELISA at 28 days post booster [Day 28]
Assess and compare humoral immune response from a fractional vs. full booster dose of BNT162b2 or AZD1222 in immunocompetent adults fully primed with BNT162b2, AZD1222, or Sinovac vaccines or natural infection, measured by anti-Spike IgG binding ELISA at 28 days post booster
- Safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination [Day 28]
Describe the safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination through estimated incidence of solicited local and systemic adverse events, and incidence of unsolicited reported adverse events Occurrence of solicited local and systemic reactions within 7 days of booster Occurrence of unsolicited AEs within 28 days of booster
Secondary Outcome Measures
- Sero-response rate by anti-Spike IgG binding ELISA at 3m and 6m post booster [Month 3 and Month 6]
Assess the persistence of humoral immunity after a fractional vs. full booster dose of BNT162b2 or AZD1222 in immunocompetent adults fully primed with BNT162b2, AZD1222, or Sinovac vaccines or natural infection, measured by anti-Spike IgG binding ELISA at 3m and 6m post booster
- Safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial [Throughout study, 6 months per participant]
Describe the safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial Occurrence of Medically attended adverse reactions within 3 months of booster Occurrence of adverse events (AE), Serious adverse events (SAE), and adverse events of special interest (AESI) within 28 days, 3 months, and 6 months of booster
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy male or female individuals aged 18 years to 60 years
-
Participant is willing and able to give written informed consent for participation in the trial
-
Individuals who can comply with trial procedures and are available for the duration of follow-up.
Brazil:
● Previous vaccination with a complete primary series of Sinovac (Priming Group 1), AZD1222 (Priming Group 2), or BNT162b2 (Priming Group 3-B) at least 6 months prior to screening
Pakistan:
● Previous vaccination with a complete primary series of Sinovac (Priming Group 1) or AZD1222 (Priming Group 2) at least 6 months prior to screening, or PCR-confirmed natural infection (Priming Group 3-P) between February 2021 - 6 months prior to screening
Exclusion Criteria:
-
Has a contraindication to BNT162b2, AZD1222 or Sinovac
-
Has received an incomplete primary COVID-19 vaccination series
-
Has received 3 doses of COVID-19 vaccine
-
Has received heterologous primary COVID-19 vaccination series
-
History of a solid organ or bone marrow transplant
-
History of malignancy (other than non-melanoma skin cancer) within the past five years
-
Currently on hemodialysis
-
Any confirmed or suspected immunosuppressive or immunodeficiency condition or diagnosis
-
On chronic (>30 days) use of immunosuppressive medications at the time of enrollment (except topical steroids or short-term oral steroids, i.e., ≤14 days)
-
Known diagnosis of HIV with CD4 count <200 cells/mm3 (in the past 6 months)
-
Active or history of previous auto-immune neurological disorders (e.g., multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) (excluding Bell's palsy)
-
Has received anti-CD20 monoclonal antibodies for any reason in the past 12 months
-
Has received monoclonal antibodies to treat a previous COVID-19 event
-
Pregnant at screening
-
Positive SARS-CoV-2 Antigen test in respiratory specimen at screening
-
Planning to migrate out of the study area within 6 months of the enrollment
-
Participants currently enrolled in any other COVID-19 vaccine research trial in which they are getting a COVID-19 vaccine during the study period
-
Illiterate individuals (Brazil only)
-
Has a severe and/or uncontrolled comorbidity
Pakistan (natural infection Priming Group (Priming Group 3-P)):
● Prior vaccination with ANY vaccine against COVID-19
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | FIOCRUZ | Campo Grande | MS Do Sul | Brazil | |
2 | Aga Khan University Clinical Trials Unit | Karachi | Sindh | Pakistan |
Sponsors and Collaborators
- Albert B. Sabin Vaccine Institute
- Aga Khan University
- Oswaldo Cruz Foundation
- Stanford University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Sabin CoV 22