Sequential vaccination against Streptococcus pneumoniae appears as immunologically safe in clinically stable kidney transplant recipient

Infections and rejection of the allograft are two major problems in organ transplant recipients. Vaccination against Streptococcus pneumoniae is recommended in this risk group, to reduce morbidity and mortality from invasive pneumococcal disease. Currently, sequential vaccination against pneumococci is recommended, consisting of vaccination with a 13-valent conjugate vaccine, followed by a 23-valent polysaccharide vaccine. Data on alloantibodies after sequential pneumococcal vaccination are still lacking.

In the current study, we sequentially determined HLA class I and II and MICA antibodies in 41 clinically stable kidney transplant recipients prior to and after first and second vaccination against pneumococci, comprising a 12-months period. Antibodies were measured by Luminex mixed bead assay. We summed up the score values of each bead (1=negative, 4=undetermined and 8=positive) for HLA class I, HLA class II or MICA, respectively; yielding antibody score values of 12–96, 5–40 or 2–16, and we added MFI values for the respective beads. In parallel, pneumococcal IgG antibodies were determined by ELISA.

During the 12-months period the sequential analysis yielded no significant change in HLA class I and II and MICA antibodies, irrespective of how the data were quantified (Figure 1).

Figure 1: Antibodies prior to and after sequential pneumococcal vaccination in 41 kidney transplant recipients.

One patient developed de novo donor-specific antibodies (DSA) 1.5 months after first vaccination (MFI 1600), but no allograft rejection was detected in this patient. A biopsy proven rejection was detected 7 months after the first vaccination in another patient (histopathological: borderline rejection with Banff category 3), who did not develop de novo DSA. Both showed a minor increase in HLA class I and II antibodies at month 1. As expected, pneumococcal antibodies showed a significant increase already at month 1 after vaccination (p = 0.0006) and the increase was even stronger at month 6, 7 and 12 (p < 0.0005).

In conclusion, HLA class I and II and MICA antibodies remained overall constant after sequential pneumococcal vaccination. Considering the general risk of alloimmune processes in solid organ transplant recipients, we would not attribute the de novo DSA or borderline rejection that occurred in 2 of 41 patients to the administered vaccines. Therefore, we consider the sequential administration of both vaccines in our cohort to be immunologically safe.

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