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.