key: cord-0866008-k5b0yg6s authors: Seija, Mariana; Rammauro, Florencia; Santiago, José; Orihuela, Natalia; Zulberti, Catherine; Machado, Danilo; Recalde, Cecilia; Noboa, Javier; Frantchez, Victoria; Astesiano, Rossana; Yandián, Federico; Guerisoli, Ana; Morra, Álvaro; Cassinelli, Daniela; Coelho, Cecilia; de Aramburu, Belén; González-Severgnini, Paulina; Moreno, Romina; Pippolo, Aldana; López, Gabriela; Lemos, Mónica; Somariva, Lorena; López, Eliana; Fumero, Soledad; Orihuela, Carla; Rodríguez, Rosalía; Acuña, Gonzalo; Rabaza, Victoria; Perg, Nancy; Cordero, Rossana; Reisfeld, Cristina; Olivera, Paula; Montero, Paola; Nogueira, Cecilia; Nalerio, Catheryn; Orihuela, Sergio; Curi, Lilián; Burgstaller, Ema; Noboa, Oscar; Pritsch, Otto; Nin, Marcelo; Bianchi, Sergio title: Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant date: 2021-12-27 journal: Clin Kidney J DOI: 10.1093/ckj/sfab291 sha: 86d01ce91867211b2ce8904243be5dc397c8fcf9 doc_id: 866008 cord_uid: k5b0yg6s BACKGROUND: Antibody response against SARS-CoV-2 after mRNA or adenoviral vector based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (Coronavacࣨ) and BNT162b2 mRNA. METHODS: A national multicenter cross-sectional study was conducted. The study group was composed of patients from all KT centers in Uruguay, vaccinated between May 1(st)-May 31(st) (Coronavacࣨ n = 245 and BNT162b2 n = 39). Control group was constituted by 82 healthy individuals. Participants had no prior confirmed COVID-19 test. Blood samples were collected between 30 and 40 days after second dose. Serum specific IgG antibodies against Receptor Binding Domain (RBD) of SARS-CoV-2 Spike protein were determined using COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion [36.5% BNT162b2, 27.8% inactivated virus, p = 0.248] in comparison to 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [173 (73–554) and 29 (11–70) BAU/mL, p < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209–335) and BNT162b2: 2638 (2608–3808) BAU/mL, p < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, eGFR and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need of strategies to improve immunogenicity in KT recipients after two doses of either vaccine. Hence, vaccination in this population is recommended. Recent evidence suggests that antibody response among solid organ transplant (SOT) patients is weak after 2 doses of mRNA-based vaccine or adenoviral vector platform 6, 7, [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] . However, only one study has addressed humoral response after inactivated virus-based vaccine in KT patients 24 . Inactivated virus vaccines are a well-known technology and have several advantages for large-scale utilization, including their stability at non-extreme refrigeration temperatures and their long lifespan 25 . These characteristics make them a useful tool in the global fight against COVID-19, although more data are needed on its efficacy in KT recipients. Furthermore, recently it has been approved by EMA for emergency use in Europe and to date, more than 750.000.000 has been administrated in more than 40 countries 26, 27 . Figure 1A ). Serum levels of anti-RBD IgGs were significantly higher in KT patients who received BNT162b mRNA compared with inactivated virus vaccine, with a median of 173 (73-554) and 29 (11-70) BAU/mL respectively (p<0.034, Figure 1B ). Compared to healthy control group, KT had lower levels of antibody with either vaccine. Seropositive patients for anti-RBD were significantly younger, had higher eGFR and lymphocyte count, as well as longer time since transplantation. In regard of immunosuppression treatment, these patients were less frequently on triple therapy (antimetabolite, calcineurin inhibitor and prednisone) and more on everolimus treatment (Table 1) . In multivariate analysis, variables associated with negative humoral response were age (per ten years, odds ratio 1. were no severe side-effects reported in this cohort ( Figure 2 ). These findings agree with previous studies that report a seroconversion between 10% and 40% with mRNA-based vaccine 6 COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium COVID-19-related mortality in kidney transplant and dialysis patients: Results of the ERACODA collaboration Respiratory and Gastrointestinal COVID-19 Phenotypes in Kidney Transplant Recipients COVID-19 infection in kidney transplant recipients: Disease incidence and clinical outcomes Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe Antibody response to 2-dose sars-cov-2 mrna vaccine series in solid organ transplant recipients mRNA Vaccine in a Cohort of Hemodialysis Patients and Kidney Transplant Antibody response to SARS-CoV-2 mRNA BNT162b2 vaccine in kidney transplant recipients and in-centre and satellite centre haemodialysis patients SARS-CoV-2 breakthrough infections in vaccinated kidney transplant recipients: an issue of concern Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine Impaired humoral response in renal Clinical Impact, Reactogenicity, and Immunogenicity After the First CoronaVac Dose in Kidney Transplant Recipients COVID-19 vaccines: modes of immune activation and future challenges Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile Effectiveness of an Inactivated SARS-CoV-2 Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses Weak antibody response to 3 doses of mRNA vaccine in kidney transplant recipients treated with belatacept Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients Lymphocyte count, cells/L, median (IQR) Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate using CKD EPI Formula Receptor Binding Domain of SARS-CoV-2 spike protein; SD, standard deviation