An open label, uncontrolled clinical trial of immunogenicity and safety of yellow fever vaccine in adults with chronic kidney disease as compared to immunocompetent

INTRODUCTION: During a yellow fever (YF) epidemic in Brazil, vaccination campaigns targeting the entire population in the affected areas were conducted, bringing up an opportunity to prospectively evaluate YF vaccine's immunogenicity and safety in adults with chronic kidney disease (CKD). METHODS: Open-label, uncontrolled clinical trial involving adults aged ≥18 years with CKD on dialysis (CKD-D) or not (CKD-ND) and immunocompetent, who had denied previous YF vaccination. All of them received a YF vaccine standard dose (0.5 mL). Neutralizing antibodies were measured by microneutralization test with 50% reduction of lysis plaques (micro-PRN50) 10, 30 and 365 days after vaccination. Viremia was evaluated by RT-PCR. Adverse events following immunization (AEFI) were monitored. Primary outcomes were seropositivity and seroconversion rates. Secondary outcomes were antibody geometric mean titers (GMT) and safety. RESULTS: 154 participants were included: 54 CKD-D, 41 CKD-ND and 59 immunocompetent. Median age was 50, 61 and 47 years, respectively. Ten days after vaccination (D10), seropositivity was significantly lower in CKD (CKD-ND, 62.5%; CKD-D, 48%) than in immunocompetent (86.7%) and CKD had lower GMT. On D30, GMT increased in all groups, without significant differences on seropositivity and GMT between groups. On D365, GMT decreased, but most participants persisted seropositive, without significant differences. On D10, viremia was detected in 28.8% of CKD-D; 32.3% of CKD-ND, and 28.9% of immunocompetent, without significant difference between groups. The CKD participants had lower viremia. Immunocompetent participants more frequently reported AEFI (66.7%) than CKD-ND (48.5%) and CKD-D (48.8%). Most common AEFI were headache (32.7%), myalgia (28.4%) and injection site pain (25.3%). CONCLUSIONS: Adults with CKD had a robust although delayed neutralizing antibody response to YF vaccine and the vaccine was well-tolerated. The small sample size precluded the detection of small differences in immune response between the groups and the occurrence of rare serious AEFI related to YF vaccine.