Immune Response to the 23-Valent Polysaccharide Pneumococcal Vaccine (PPV23) after the 7-Valent Conjugate Vaccine (PCV7) in Allogeneic Stem Cell Transplant (SCT) Recipients: Results of the EBMT IDWP01 Trial
Authors: Cordonnier Catherine , Labopin Myriam , Chesnel Virginie , Ribaud Patricia , De La Camara Rafael , Martino Rodrigo , Ullmann Andrew , Parkkali Terttu , Locasciulli Anna , Yakouben Karima , Pauksens Karlis , Einsele Hermann , Niederwieser Dietger , Apperley Jane , Ljungman Per T. 
Published: April 2020

Abstract
Background: Pneumococcal infections are causes of death after SCT. The IDWP01 trial compared early (E) vs late (L) pneumococcal immunization after allogeneic SCT, starting either at 3, or at 9 months post-transplant with 3 doses of PCV7 given at 1 month intervals,. This study has shown that the early immunization was not inferior in the proportion of responders one month after the last PCV7 dose. In addition, all patients received one dose of PPV23 after the 3 doses of PCV7 at 12 months and 18 months in the E and L groups, respectively. The goal of this supplementary analysis was to look at the immune response to the PPV23 according to the time of its administration.
Methods: 158 patients were randomized in the IDWP01 trial, 75 in the E, and 83 in the L group, of whom 109 received the PPV23 (56 in the E, and 53 in the L group, respectively) and 86 (44 in the E, and 42 in the L group) were followed up to 24 months after SCT. The immune response to PPV23 was assessed by the antibody (Ab) titres, measured by ELISA to pn1 and pn5, which are both included in PPV23 but not in PCV7. Pn1 and pn5 Ab titres were assessed before, and one month after the PPV23 dose, and at 24 months post-SCT. Two cut-off levels for protection were considered for each antigen: □ .15 μg/ml and □ .5 μg/ml. The geometric mean concentrations (GMC) were also analyzed. Additionally, all Ab titres to the 7 PCV7 antigens were measured in parallel.
Results: Ab titres to pn1 and pn5 before the PPV23 were not significantly different in the E (at 12 mo post-SCT) and in the L (at 18 mo post-SCT) group. Whatever the cut-off used to evaluating the response, the percentage of responders one month after the PPV23 was not significantly different in both groups: For pn1: □ .15μg/ml: E: 80% vs L: 87%; □ .5μg/ml: E: 42% vs L: 60%; For pn5: □ .15μg/ml: E: 84% vs L: 94%; □ .5μg/ml: E: 62% vs L: 74%). The GMC were not significantly different in the E vs. the L group for pn1. The GMC were significantly higher in the L vs. the E group for pn5 (P=.02). At 24 months post-SCT, there was no significant difference in the GMC of pn1 and pn5 Ab titres but there was a tendency for higher titres in the L group for both antigens. Additionally, among 36 non-responders to the PCV7 at the time of PPV23 administration, 21 remained non-responders, but 15 (42%) responded to all the seven PCV7 antigens 1 month later.
Conclusion: Although there was a tendency for a better response rate and for higher GMC for pn1 and pn5 according to the timing of immunization with PPV23 (12 vs. 18 months) in favour of the L group, these differences were not significant. Additionally, PPV23 increase the response rate to the serotypes included in the PCV7. Therefore, we recommend starting PCV7 vaccination early after SCT (3 PCV7 from 3 months). A dose of PPV23 after 3 doses of PCV7 broadens the immune response to pneumococci as well as increases the response rate to the serotypes included in the PCV7 and should therefore be considered at 12 months after SCT.
The authors are grateful to the Safety committee: D Engelhard, P Reusser, and P Reinert