Abrogation of potent humoral vaccine responses in patients on long-term anti-CD25 therapy (B196)

Abstract

Abstract Daclizumab, a monoclonal antibody that binds CD25, has been effective in the treatment of a number of autoimmune diseases. Despite continuous IL-2 receptor blockade for extended periods in these patients, there have been no instances of opportunistic infection and the rate of community-acquired infections is no greater than that of the general populace. This suggests that daclizumab dosing is balanced between prevention of autoimmunity and susceptibility to infection. To test this hypothesis, as a surrogate for infection we measured hepatitis vaccine responses in five patients with autoimmune uveitis who had been on daclizumab therapy for as long as 92 months. Surprisingly, only one equivocal vaccine response was observed. Given the high frequency of seroconversion (>95%) induced by these vaccines in healthy adults, this study is sufficiently powered to demonstrate statistically significant differences from the expected hepatitis vaccine response rate (p=0.0005). These results show that daclizumab can block the response to a potent immunogen in vivo. Given that alum based vaccine responses are highly dependent on IL-4, the known inhibition of Th2 cytokine production by daclizumab is likely to have contributed to the vaccine failures we observed. Our results indicate that, where possible, antibiotic/antiviral drug prophylaxis may be preferable to vaccination in patients on daclizumab therapy.