Three doses of a recombinant conjugated SARS-CoV-2 vaccine early after allogeneic hematopoietic stem cell transplantation: predicting indicators of a high serologic response-a prospective, single-arm study.

Background: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-binding domain (RBD)-tetanus toxoid (TT)-conjugated platform shortly after allo-HSCT in the developing country of Iran. Methods: This prospective, single-arm study aimed to investigate immunogenicity and its predictors following a three-dose SARS-CoV-2 RBD-TT-conjugated vaccine regimen administered at 4-week (± 1-week) intervals in patients within 3-12 months post allo-HSCT. An immune status ratio (ISR) was measured at baseline and 4 weeks (± 1 week) after each vaccine dose using a semiquantitative immunoassay. Using the median ISR as a cut-off point for immune response intensity, we performed a logistic regression analysis to determine the predictive impact of several baseline factors on the intensity of the serologic response following the third vaccination dose. Results: Thirty-six allo-HSCT recipients, with a mean age of 42.42 years and a median time of 133 days between hematopoietic stem cell transplant (allo-HSCT) and the start of vaccination, were analyzed. Our findings, using the generalized estimating equation (GEE) model, indicated that, compared with the baseline ISR of 1.55 [95% confidence interval (CI) 0.94 to 2.17], the ISR increased significantly during the three-dose SARS-CoV-2 vaccination regimen. The ISR reached 2.32 (95% CI 1.84 to 2.79; p = 0.010) after the second dose and 3.87 (95% CI 3.25 to 4.48; p = 0.001) after the third dose of vaccine, reflecting 69.44% and 91.66% seropositivity, respectively. In a multivariate logistic regression analysis, the female sex of the donor [odds ratio (OR) 8.67; p = 0.028] and a higher level donor ISR at allo-HSCT (OR 3.56; p = 0.050) were the two positive predictors of strong immune response following the third vaccine dose. No serious adverse events (i.e., grades 3 and 4) were observed following the vaccination regimen. Conclusions: We concluded that early vaccination of allo-HSCT recipients with a three-dose RBD-TT-conjugated SARS-CoV-2 vaccine is safe and could improve the early post-allo-HSCT immune response. We further believe that the pre-allo-HSCT SARS-CoV-2 immunization of donors may enhance post-allo-HSCT seroconversion in allo-HSCT recipients who receive the entire course of the SARS-CoV-2 vaccine during the first year after allo-HSCT.

Evaluation of Safety and Immunogenicity of a Recombinant Receptor-Binding Domain (RBD)-Tetanus Toxoid (TT) Conjugated SARS-CoV-2 Vaccine (PastoCovac) in Recipients of Autologous Hematopoietic Stem Cell Transplantation Compared to the Healthy Controls; A Prospective, Open-Label Clinical Trial.

Background: The urgent need for prompt SARS-CoV-2 immunization of hematopoietic stem cell transplant (HSCT) recipients in an endemic area raises many challenges regarding selecting a vaccine platform appropriate for HSCT recipients being economical for widespread use in developing countries. Methods: The trial is a prospective, single-group, open-label study to investigate the safety and serologic response of two doses of the recombinant receptor-binding domain (RBD)-Tetanus Toxoid (TT) conjugated SARS-CoV-2 vaccine (PastoCovac) early after autologous (auto) HSCT. For this reason, a total of 38 patients who completed the two-dose SARS-CoV-2 RBD-based vaccine between three to nine months after auto-HSCT and had an available anti-spike serologic test at three predefined time points of baseline and after the first and second doses and 50 healthy control individuals were included in the analysis. The primary outcome was defined as an increase in IgG Immune status ratio (ISR) to the cut-off value for the positive result (≥1.1) in the semiquantitative test. Findings: The median time between auto-HSCT and vaccination was 127 days. No participant reported any significant adverse effects (Grade 3). Pain at the injection site was the most common adverse event. The ISR increased significantly (p < 0.001) during the three-time point sampling for both patients and healthy control groups. In patients, the mean ISR increased from 1.39 (95% CI: 1.13−1.65) at baseline to 2.48 (1.93−3.03) and 3.73 (3.13−4.38) following the first and second dosages, respectively. In multivariate analysis, the higher count of lymphocytes [OR: 8.57 (95% CI: 1.51−48.75); p = 0.02] and history of obtaining COVID-19 infection before transplantation [OR: 6.24 (95% CI: 1.17−33.15); p = 0.03] remained the predictors of the stronger immune response following two doses of the RBD-TT conjugated vaccine. Moreover, we found that the immunogenicity of the COVID-19 vaccine shortly after transplantation could be influenced by pre-transplant COVID-19 vaccination. Interpretation: The RBD-TT conjugated SARS-CoV-2 vaccine was safe, highly immunogenic, and affordable early after autologous transplants. Funding: This work was mainly financed by the Hematology-Oncology-Stem Cell Transplantation Research Center (HORCSCT) of Tehran University and the Pasteur Institute of Iran.