Purpose: This study aims to compare the immunogenicity of a third dose of the heterologous BNT262b2 mRNA vaccine versus the homologous inactivated whole-virion CoronaVac vaccine in adult kidney transplant recipients (KTR).

Methods: This prospective, single-center, phase 4 interventional study included KTR aged 30-69 years, with more than 30days of transplantation and no previous confirmed COVID-19. At the transplant center, the patients received the 3rd heterologous (BNT162b2 mRNA) or homologous dose at least four weeks after the standard two-dose schedule of the CoronaVac vaccine. Antibody response immediately before and after the 3rddose was assessed by the AdviseDx SARS-CoV-2 IgG II assay. For those positive assays, neutralizing anti-SARS-CoV-2 antibodies were evaluated by the cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit.

Results: There were 307 patients in the heterologous group and 777 in the homologous group. KTR in the heterologous group were older (median age 54 vs. 50 years,p<0.0001), with a lower prevalence of diabetes (7% vs. 11%,p=0.032), lower percentage of deceased donors (60% vs. 68%,p=0.006) and longer time since transplant (median 11 vs. 6 years,p< 0.0001). Immediately before the 3rd dose, seroprevalence for IgG antibodies (36% vs. 34%,p=0.597) and the median antibody titers among those seroprevalent (246 AU/mL vs. 268 AU/mL,p=0.279) were similar. At a median of 25 days after the heterologous and 35 days after the homologous 3rddose vaccine, seroconversion rate was higher in the heterologous group (49% vs. 32%,p<0.0001), resulting in a higher seroprevalence rate (67% vs. 55%,p=0.0003). Overall, 42% remained seronegative after the third dose. In addition, the median antibody titers after booster among those seroprevalent patients were higher in those in whom the 3rd heterologous vaccine was administered (7,771 AU/mL vs. 599 AU/mL,p<0.0001). The analysis of the neutralizing activity is ongoing.

Conclusion: This prospective interventional study suggests that a third heterologous dose is associated with a higher seroconversion rate and median antibody titers compared to a homologous dose in kidney transplant recipients fully vaccinated with inactivated whole-virion CoronaVac vaccine. In addition, 42% of subjects did not produce a humoral immune response after the third dose, urging the development of alternative strategies.