Sequential Vaccination Against Streptococcus pneumoniae Appears as Immunologically Safe in Clinically Stable Kidney Transplant Recipients

<b>Background:</b> Vaccination against <i>Streptococcus pneumoniae</i> is advised for transplant recipients to reduce morbidity and mortality associated with invasive pneumococcal disease. However, data on alloantibodies after sequential vaccination (with a pneumococcal conjugate vaccine followed by a polysaccharide vaccine) are still lacking. <b>Methods:</b> In the current study, we determined HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies in 41 clinically stable kidney transplant recipients. These antibodies were measured prior to and post sequential pneumococcal vaccination over a period of 12 months. Alloantibodies were measured by Luminex bead-based assays, and pneumococcal IgG antibodies were measured by ELISA. <b>Results:</b> Over a 12-month period, the sequential analysis revealed no significant change in alloantibodies. One patient developed de novo donor-specific antibodies (DSA) 1.5 months after the first vaccination, with mean fluorescence intensities of up to 2300. These DSA became undetectable in the follow-up, and the patient showed no signs of allograft rejection. Another patient experienced a biopsy-proven borderline rejection 7 months after the first vaccination but did not develop de novo DSA. Both maintained stable kidney function. As expected, the pneumococcal antibodies increased significantly after vaccination (<i>p</i> < 0.0001). <b>Conclusions:</b> Given the overall risk of alloimmune responses in transplant recipients, we would not attribute the two noticeable patient courses to vaccination. Thus, we consider sequential vaccination immunologically safe.