COVID-19 Vaccines, Hematopoietic Stem Cell Transplantation (HSCT), Immune System Tolerance
Conditions
Keywords
hematopoietic stem cell transplantation, SARS-CoV-2 specific IgG , immune reconstitution, COVID-19 vaccine efficacy
Brief summary
COVID-19 vaccinations are predicted to be a huge success in pandemic control. However, the majority of the studies were conducted on healthy individuals, and the efficiency of COVID-19 vaccination in post-transplant patients is uncertain. In the setting of HSCT, the extreme immunosuppression caused by the conditioning regimen and the graft versus host disease (GvHD) preventive regimen clearly has an impact on the efficacy and immunogenicity of the COVID-19 vaccine. Given the importance of eliciting early SARS-Cov-2 protective immunity in patients who are undergoing Allo-HSCT and the EBMT recommendation to endorse vaccination as early as 3 months after allo-HCT \[7\], we conduct this prospective study to investigate the safety and immunogenicity of three doses Pastucovac (an RBD-based SARS-Cov-2 vaccine) at the early post-transplant period in adult Iranian patients who are undergoing Allo-HSCT. We also want to see whether there are any possible predictors, such as the effect of clinical characteristics and lymphocyte subpopulations at the time of vaccination on the serologic response following immunization. The findings of this study will serve to guide future COVID-19 vaccination recommendations in this population, such as the optimal starting time, interval time, and so on.
Detailed description
From the start of the study until the sample size of 100 patients is attained, all consecutive adult patients who are candidates for Allo-SCT at HORCSCT, sign a research project consent to administer SARS-CoV-2 vaccination with Pastucovac, and sign a permission to take pre-and post-vaccination blood samples for deposit to the research database, are enrolled in the study. At baseline (before conditioning) and day +30 post-transplant, peripheral blood samples are taken to test particular lymphocyte subpopulations and SARS-CoV-2 IgG titers. All enrolled post-Allo-SCT participants who meet the inclusion criteria including; age ≥ 18 years, successfully engraftment with full donor chimerism, absence of grade 3,4 acute GvHD or severe extensive chronic GvHD, no receive more than 0.5 mg/kg prednisolone, and no positive RT-PCR test for COVID-19 following HSCT are recruited to study from 3 to 12 months after Allo-HSCT and vaccinated with 2 doses of Pastucovac, with a 4-week (±7 days) interval and a booster dose with an 8-week (±7 days) interval from the second dose. Peripheral blood samples are collected before the first dose of vaccine to assess certain immune reconstitution and SARS-CoV-2 IgG titer. The serologic response against the SARS-CoV-2 spike protein (anti-S) is assessed in serum four weeks (± one week) after the first vaccine dose (before the second vaccine), four weeks (± one week) after the second dose, and four weeks (± one week) after the booster dose (third dose).
Interventions
BIOLOGICALPasocovac vaccine
All enrolled post-Allo-SCT participants who meet the inclusion criteria are recruited to study from 3 to 12 months after Allo-HSCT and vaccinated with 2 doses of Pastucovac, with a 4-week (±7 days) interval and a booster dose at an 8-week (±7 days) interval from the second dose.
Sponsors
Tehran University of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Age ≥ 18 years, successfully engraftment with full donor chimerism, absence of grade 3,4 acute GvHD or severe extensive chronic GvHD, no receive more than 0.5 mg/kg prednisolone, and no positive RT-PCR test for COVID-19 following HSCT
Exclusion criteria
Patients who are not candidates for the COVID-19 vaccine after transplantation due to severe complications. Patients who do not consent to vaccination after transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of COVID-19 vaccine effectiveness | 4 weeks (±7 days) post second COVID-19 vaccine | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer |
| Grade III-IV vaccine-related adverse reactions | 14 days after administration of each vaccine dose | Prevalence of reactogenicity, Serious Adverse Events (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune cells recovery predicting the response to the COVID-19 vaccine | 4-week (±7 days) after third (booster) dose of vaccine. | Measuring how early post HSCT Immune subsets reconstitution including T cells, NK cells, and B cells predict the seroconversion after second dose of vaccine. |
| seroconversion after second dose of vaccine | 4-week (±7 days) after second dose of vaccine. | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer in patients starting their vaccination course 3-6 months after HSCT |
| seroconversion after first dose of vaccine | 4-week (±7 days) after first dose of vaccine. | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer |
| Incidence of Acute Graft versus host disease (GvHD) | 4-week (±7 days) after second and third (booster) dose of vaccine. | Measuring how the acute GvHD affect the response to the vaccine |
| Incidence and severity of COVID-19 infections | 6 months following start of immunization | Determine incidence and severity of COVID-19 infections by 6 months following immunization with a SARS-CoV-2 vaccine. |
| Correlation of seroconversion with patient characteristics | 4-week (±7 days) after second and third (booster) dose of vaccine. | Determine how the patients characteristics including age, sex, performance score, and underlying disease affect on seroconversion |
| seroconversion after third (booster) dose of vaccine | 4-week (±7 days) after third (booster) dose of vaccine. | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer |
| GvHD prophylactic strategy affect immunological response | 4-week (±7 days) after third (booster) dose of vaccine. | Measuring how early prophylactic immuno-suppression tapering affect the response to the vaccine |
Countries
Iran
Contacts
Primary ContactMaryam Barkhordar, MD
Backup ContactLeila Sharifi Aliabadi, Master
Outcome results
None listed