Theoretically, exposure to multiple viral antigens from an inactivated virus vaccine could trigger a stronger induction of neutralizing antibodies. seronegative. Antibody titers after booster in seropositive patients were higher in the heterologous group (7771 versus 599 AU/mL; < 0.0001). These Rabbit Polyclonal to Tau (phospho-Ser516/199) results persisted after adjusting for confounding variables. Lastly, a similar proportion of patients became seropositive for neutralizing antibodies (98% versus 94%; = 0.098). Conclusions. In kidney transplant recipients fully vaccinated with CoronaVac, a CL-82198 third dose with an mRNA vaccine produced CL-82198 a higher seroconversion rate and antibody titers than a third homologous dose. However, both boosters achieved equivalent seroprevalence for neutralizing antibodies. The high proportion of still seronegative patients indicates the need for alternative strategies of protection. INTRODUCTION Kidney transplant recipients achieve seroprevalence rates between 3% and 59% 4 wk after 2 doses of mRNA, viral vector, or inactivated whole-virion vaccines,1-4 which is lower than the general population.5,6 Developing a humoral immune response is associated with protection against breakthrough infections because more severe disease and deaths concentrate among seronegative patients.3,4,7 Thus, it seemed reasonable to apply additional doses of vaccine to achieve immunization in transplanted patients, who are at higher risk for coronavirus disease 2019 (COVID-19)Crelated mortality.8 The first attempts were to administer homologous boosters to seronegative patients after the full 2 doses of vaccination. However, in a French cohort, only 44% of the 59 solid organ transplant recipients who had been seronegative developed antibodies after a third homologous dose of the BNT162b2 mRNA vaccine.9 Similarly, we have observed a low seroconversion rate of 20.3% after a third homologous dose of the CoronaVac vaccine in those seronegative kidney transplant recipients.10 In the general population, initiated from safety considerations associated with the Oxford-AstraZeneca ChAdOx1-S (AZD1222) vaccine, mixing with mRNA vaccines ultimately has produced evidence in favor of a similar or even superior humoral and cellular response and clinical effectiveness compared to those with the homologous prime boosters.11-15 In the transplant population, a small German study including 40 kidney transplant recipients and 70 immunocompetent controls found that heterologous boosting with mRNA after vector vaccine priming was the regimen that produced the most robust humoral and cellular response.16 The little experience on heterologous boosters in kidney transplant recipients is restricted to endogenous antigen platform vaccines, either viral vector or mRNA. Theoretically, exposure to multiple viral antigens from an inactivated virus vaccine could trigger a stronger induction of neutralizing antibodies. Additionally, there are few studies systematically comparing the effect of a heterologous versus a homologous third dose. In this analysis, we compared the seroconversion rates after a heterologous third dose of the BNT262b2 mRNA vaccine versus a homologous third dose of the CoronaVac inactivated whole-virion vaccine after the former 2-dose CL-82198 schedule of CoronaVac. Additionally, we evaluated the increased rate in antibody titers and neutralizing activity after heterologous BNT162b2 versus homologous CoronaVac third doses. We also described the occurrence and severity of breakthrough infections up to 3 mo after the third dose. Finally, we investigated independent factors for seroconversion after the third dose, high antibody values, and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination. MATERIALS AND METHODS Study Design This is a prospective single-center cohort study derived from the previously published original trial in that kidney transplant recipients received 2 doses of the inactivated CoronaVac vaccine.17 The conception of the present study was driven by the urge of giving to the largest number of patients as soon as possible an additional vaccine dose against coronavirus, following the National Guidelines. Therefore, no prior hypothesis was conceived, and no sample size was determined on advance. This study protocol was approved by the local ethics committee, and the patients signed an updated informed consent form. Inclusion criteria CL-82198 consisted of kidney transplant recipients aged 30C69 y, CL-82198 with >30 d of transplant,.