Evaluation of the serological response to the heterologous versus homologous booster vaccinationin in patients receiving autologous hematopoietic stem cell transplantation

Comparing safety and serological response following homologous vs. heterologous COVID-19 booster vaccine in patients receiving autologous hematopoietic stem cell transplants(AHSCT)

This is a phase 2-3 double-blind, randomized controlled clinical trial to compare the serological response of the homologous COVID-19 vaccine versus the heterologous booster dose in 90 adult patients receiving AHSCT. For randomization, a balanced block randomization list was generated using the research institute's Web-based software, after entering the sample size and number of each block.

Eligible adult patients receiving AHSCT in a research institute for oncology, hematology, and cell therapy, will be invited four weeks (±7 days) after the 2nd dose. After obtaining the written informed consent, COVID-19 rapid test and antibody titer test will be performed, afterward, the national code enter into the system, and the vaccine code will be announced. The vaccine will be injected. Antibody titer and Side effects are evaluated four weeks (±7 days) after the vaccination.

Inclusion criteria: Age: 18-70 Time interval: 6 to 12 months after AHSCT Receiving two doses of Pastocovac vaccine, Exclusion criteria: Relapse of underlying disease

Group A is a homologous vaccine (Pastocovac), and group B is a heterologous vaccine (Sinopharm ). In both groups, the rapid COVID-19 test will be performed, and then the blood sample will be tested to measure the COVID-19 antibody titer. The patient will randomly receive the vaccine, and after four weeks (±7 days), the patient's blood sample will test for antibody titer, and the vaccine's side effects will be recorded.

SARS-CoV-2 Anti SPIKE IgG titer three weeks (±7 days) following homologous versus heterologous booster vaccine

Recruitment has been completed. Trial has already been completed

Assigning to the study groups is a parallel; group A is considered the intervention group of homologous vaccine (Pastocovac vaccine), and group B is the intervention group of heterologous vaccine (Sinopharm vaccine). The balanced block randomization list will be generated through the research institute's web-based software; after entering the sample size 90 and considering the block size of 4, according to this balanced block randomization list, a sequence of numbers is created, and this sequence of numbers is defined in the system. If the patients meet the criteria of the study after obtaining informed consent, their national code will be entered into the system, and the software will announce the code of each patient. Patients receive one of two vaccines randomly.

Due to ethical considerations, a placebo arm will not be used. 10-dose vials of both types of vaccines are given to a person outside the research team. At pre-determined times when some patients come to inject a booster dose, each vial of 10-dose Sinopharm or Pastocococ vaccine is poured into ten insulin syringes as a single dose by the responsible person and is coded by the sequence of numbers according to a random list and considering the cold chain. The code label has already been prepared and is provided to that person. Coded vaccine syringes will be placed in a special refrigerator at a temperature of 2-4 degrees until the time of injection, which should be half an hour. Apart from the above person, all the research team members, including the Care provider, the person responsible for injecting the vaccine, the person responsible for collecting information, the analyst, and the patient, are not aware of the type of vaccine.

Background/Purpose: Optimizing vaccine efficacy is of particular concern in patients undergoing hematopoietic stem cell transplantation (HSCT), which mainly have an inadequate immune response to primary SARS-CoV-2 vaccination. This investigation aimed to explore the potential prime-boost COVID-19 vaccination strategies following autologous (auto-) HSCT. Methods: In a randomized clinical trial, patients who had already received two primary doses of receptor-binding domain (RBD) tetanus toxoid (TT) conjugated SARS-CoV-2 vaccine during three to nine months after auto-HSCT were randomized to receive either a homologous RBD-TT conjugated or heterologous inactivated booster dose four weeks after the primary vaccination course. The primary outcome was comparing the anti-S IgG Immune status ratio (ISR) four weeks after the heterologous versus homologous booster dose. The assessment of safety and reactogenicity adverse events was considered as the secondary outcome.(IRCT Id IRCT20140818018842N24) Results: Sixty-one auto-HSCT recipients were recruited and randomly assigned to receive either homologous or heterologous booster doses four weeks after the primary vaccination course. The mean ISR was 3.40 (95% CI: 2.63- 4.16) before the booster dose with a 90.0% seropositive rate. The ISR raised to 5.12 (95% CI: 4.15- 6.08) with a 100% seropositive rate after heterologous (P= 0.0064) and to 3.42 (95% CI: 2.67- 4.17) with a 93.0% seropositivity after the homologous booster doses (P= 0.96). In addition, the heterologous group suffered more AEs following the booster dosage than the homologous group, but this difference was not statistically significant (p = 0.955). In multivariable analysis, the primeboost vaccination strategy (heterologous versus homologous), the level of ISR before the booster dose, and the length of time between auto-HSCT and booster dose were the positive predictors of serologic response to a booster dose. No serious adverse event is attributed to booster vaccination. Conclusion: In patients who were primed with two SARS-CoV-2 vaccine doses during the first year after auto-HSCT, heterologous prime-boost COVID-19 vaccination with inactivated platform resulted in considerably enhanced serologic response and non-significantly higher reactogenicity adverse events than homologous RBD-TT conjugated prime-boost COVID-19 vaccination strategy. KEYWORDS SARS-CoV-2, heterologous prime boost COVID-19 vaccination, hematopoietic stem cell transplantation, RBD subunit vaccine, inactivated vaccines, immunogenicity