Humoral response to heterologous prime-booster vaccination in heart transplant recipients aged 18-70 years primed with a viral vector SARS-CoV-2 vaccine.

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster). Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay. A total of 80 heart transplant patients (mean age 49 ± 13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28-33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p < 0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p < 0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine basedregimen (p = 0.007). Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

Humoral response to SARS-CoV-2 adenovirus vector vaccination (ChAdOx1 nCoV-19 [AZD1222]) in heart transplant recipients aged 18 to 70 years of age.

BACKGROUND: Recent studies have suggested a blunted immune response to messenger RNA vaccines in solid organ transplant (SOT) recipients. Given the paucity of data on adenovirus vector vaccines use in immunosuppressed SOT recipients, we sought to describe the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in a heart transplant population. METHODS: Heart transplant recipients aged 18 to 70 years scheduled to receive 2 doses of the ChAdOx1 nCoV-19 vaccine were enrolled into a prospective study involving serum analysis to define their antibody response. An antibody concentration against the spike protein receptor-binding domain of ≥0.8 U/mL was deemed a detectable antibody response. RESULTS: A total of 99 heart transplant recipients (mean age 51 ± 12.5 years, 28% female) were enrolled. No major adverse events were recorded after vaccination; minor symptoms included injection site pain (24%), fatigue (21%) and headache (14%). Of 7 patients with prior SARS-CoV-2 confirmed by PCR testing, all (100%) had detectable antibody responses following first and second vaccine doses. In those with no prior SARS-CoV-2 infection (n = 92), 24% (n = 22) showed an antibody response after dose 1, increasing to 34.8% (n = 32) after dose 2, p < 0.001. Chronic kidney disease (CKD) stage ≥3 (OR 4.7, 95% CI 1.5-15, p = 0.009) and mycophenolate use (OR 4.1, 95% CI 1.2-14, p = 0.02) were independently associated with a nondetectable antibody response. CONCLUSIONS: Almost two-thirds of heart transplant recipients aged 18 to 70 years without a history of prior SARS-CoV-2 infection failed to develop a detectable antibody response following administration of the ChAdOx1 nCoV-19 vaccine. Patient phenotyping may help predict which patients are less likely to develop detectable antibody responses.