Latent cytomegalovirus infection and previous capsular polysaccharide vaccination predict poor vaccine responses in older adults, independent of chronic kidney disease.

BACKGROUND Patients with chronic kidney disease (CKD) are more prone to severe infection. Vaccination is a key strategy to reduce this risk. Some studies suggest vaccine efficacy may be reduced in patients with CKD, despite preserved maintenance of long-term responses to some pathogens and vaccines. Here, we investigated immune responses to two vaccines in patients with CKD in order to identify predictors of immunological responsiveness. METHODS Individuals >65 years old, with or without non-dialysis CKD (n=36 and 29, respectively), were vaccinated with a non-adjuvanted seasonal influenza vaccine (T-dependent) and Pneumovax23 (PPV23, T-independent). Humoral responses were measured at baseline, day 28 and 6 months. Lymphocyte subset and plasmacell/blast analyses were performed using flow cytometry. CMV serotyping was assessed by ELISA. RESULTS Only modest responsiveness was observed to both vaccines, independent of CKD status (25% adequate response in controls versus 12-18% in CKD group). Unexpectedly, previous immunization with PPV23 (median 10-year interval) and CMV seropositivity were associated with poor PPV23 responsiveness in both study groups (p<0.001 and 0.003 respectively, multi-variable linear regression model). Patients with CKD displayed expanded circulating populations of Th2 and Tregs, which were unrelated to vaccine responses. Despite fewer circulating B cells, patients with CKD were able to mount a similar day 7 plasmacell/blast response to controls. CONCLUSION Patients with non-dialysis CKD can respond similarly to vaccines as age and sex matched healthy individuals. CKD patients display an immune signature that is independent of vaccine responsiveness. Prior PPV23 immunization and CMV infection may influence responsiveness to vaccination.