Vaccines against SARS-CoV-2 approved for use in the UK include the mRNA vaccines Pfizer BioNTech BNT162b2 (Pfizer) and Moderna mRNA-1273,; and the Adenovirus vector vaccines Oxford-AstraZeneca ChAdOx1 nCoV-19 (AZ) and Janssen Ad26.COV2-S. Several groups have now reported around the immunogenicity of SARS-CoV-2 vaccines in immunocompromised patients. AZ. Following two vaccine doses, positive responses occurred in 96% dialysis, 52% transplant, 70% autoimmune patients and 100% of healthy controls. In dialysis patients, higher antibody responses were observed with the Pfizer vaccination. Predictors of poor antibody response were triple immunosuppression (adjusted odds ratio [aOR]0.016;95%CI0.0020.13;p< 0.001) and mycophenolate mofetil (MMF) (aOR0.2;95%CI 0.10.42;p< 0.001) in transplant patients; rituximab within 12 months in autoimmune patients (aOR0.29;95%CI 0.0080.096;p< 0.001) and patients receiving immunosuppression with eGFR 15-29 ml/min (aOR0.031;95%CI 0.110.84;p= 0.021). Lower antibody responses were associated with a higher chance of a breakthrough contamination. == Conclusions == Amongst dialysis, kidney transplant and autoimmune populations SARS-CoV-2 vaccine antibody responses are reduced compared to healthy controls. A reduced response to vaccination was associated with rituximab, MMF, triple immunosuppression CKD stage 4. Vaccine responses increased after the second dose, suggesting low-responder groups should be prioritised for repeated vaccination. Greater antibody responses were observed with the mRNA Pfizer vaccine compared to adenovirus AT101 acetic acid AZ vaccine in dialysis patients suggesting that Pfizer SARS-CoV-2 vaccine should be the preferred vaccine choice in this sub-group. Keywords:Vaccine, SARS-CoV-2, Immunosuppression, Rituximab, Mycophenolate, Transplant, Dialysis, Autoimmune, Antibody == AT101 acetic acid Introduction == The renal patient population is diverse, including individuals requiring renal replacement therapy in the form of dialysis, and those receiving immunosuppression as a result of renal transplantation or for autoimmune diseases, such as vasculitis, systemic Rabbit Polyclonal to PPM1L AT101 acetic acid lupus erythematosus (SLE) or primary glomerulonephritis (GN). SARS-CoV-2 infection is associated with high morbidity and mortality in these complex patients [1]. The vulnerability of these individuals led to public health advice for them to adopt extended protective self-isolation measures early AT101 acetic acid in the pandemic, and they were prioritised for vaccination against SARS-CoV-2. In the UK, most are being offered third doses of SARS CoV-2 vaccines in the autumn of 2021. Vaccine trials have been successful in the general population and have shown that some vaccines are up to 95% effective at preventing symptomatic infection [2,3]. However, patients with end stage kidney disease and those receiving immunosuppressive medications were largely excluded from the initial SARS-CoV-2 vaccine trials. Historically, vaccination against other infections results in suboptimal responses in these patients [46]. Vaccines against SARS-CoV-2 approved for use in the UK include the mRNA vaccines Pfizer BioNTech BNT162b2 (Pfizer) and Moderna mRNA-1273,; and the Adenovirus vector vaccines Oxford-AstraZeneca ChAdOx1 nCoV-19 (AZ) and Janssen Ad26.COV2-S. AT101 acetic acid Several groups have now reported on the immunogenicity of SARS-CoV-2 vaccines in immunocompromised patients. The serologic response to mRNA vaccines in patients receiving dialysis has been encouraging. One study, which included 1256 dialysis patients, reported seroconversion rates of 8595% after the second dose; comparable to healthy controls [7]. However, antibody titres are lower when compared with healthy controls despite high seroconversion rates [8]. Most studies have assessed the effectiveness of mRNA vaccines and few report the neutralising capacity of antibodies, but a UK multi-centre cohort study of 178 haemodialysis patients revealed that infection-nave patients had a markedly reduced neutralising antibody response to the AZ vaccine compared to the Pfizer vaccine, although the difference was reduced in individuals that experienced an infection prior to or vaccination [9]. Risk factors for reduced immunogenic response in dialysis patients included older age, co-morbidities and dialysis vintage. In contrast, antibody production after mRNA vaccination is poor in individuals with a renal transplant with less than 60% generating protective level antibodies after the second dose [9,10]. Comparison of the Pfizer and AZ vaccines in kidney transplant patients reported enhanced humoral responses with the Pfizer vaccine, however T-cell responses to both vaccines were attenuated when compared to healthy controls [11]. A reduced antibody response was associated with older age, more recent transplantation and anti-metabolite drugs, such as mycophenolate mofetil (MMF). Less data is available on patients with autoimmune disease, and disease heterogeneity makes interpretation more challenging. The OCTAVE trial is assessing SARS-CoV-2 vaccine responses (to both Pfizer and AZ vaccines) in patients with chronic immune-mediated diseases on immunosuppression including individuals with inflammatory arthritis, ANCA-associated vasculitis, inflammatory bowel disease, hepatic disease and malignancy [12]. Preliminary data indicates that although 89%.